Genetic polymorphism marker for determining pigmentation skin type and use thereof

Abstract

To provide a composition for diagnosing the presence of skin pigmentation comprising a probe capable of detecting a genetic polymorphism marker having correlation significance with the degree of skin pigmentation or a formulation capable of amplifying the marker, a kit or a microarray for diagnosing the presence of pigmentation of a skin type comprising the composition for diagnosing the presence of pigmentation of a skin type, and a method for providing information on the degree of skin pigmentation using the genetic polymorphism marker or a combination of the markers.SOLUTION: The genetic polymorphism marker having correlation significance with the degree of skin pigmentation of the present invention can provide information on the degree of an individual's skin pigmentation, and furthermore, customized components or products capable of alleviating the degree of skin pigmentation according to the information of the genetic polymorphism marker observed in the individual can be developed.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a genetic polymorphism marker having a significant association with the degree of skin pigmentation, a composition for diagnosing the presence or absence of skin pigmentation, which comprises a probe for detecting the marker or a preparation for amplifying the marker, a kit or microarray for diagnosing the presence or absence of skin pigmentation, which comprises the composition for diagnosing the presence or absence of skin pigmentation, and a method for providing information regarding the degree of skin pigmentation using the genetic polymorphism marker or a combination of markers. [Background technology]

[0002] Changes in skin pigmentation are influenced by environmental factors, age, sex, genetic mutations, and other factors. Many recent genome-wide association studies (GWAS) have reported that genetic variants in genes functionally related to the biological pathways of pigmentation are significantly associated with skin pigmentation. However, most previous GWAS studies have focused on European populations, and there have been few studies on Asian populations, so our understanding of genetic variants associated with skin pigmentation in Asian populations is limited.

[0003] The skin is the outermost layer of the human body and has various functions, such as protecting the body from harmful substances in response to the external environment and regulating body temperature through different senses. Proper functioning of the skin is essential for protecting the body from diseases and maintaining attractiveness.

[0004] Skin pigmentation types are classified into those that determine skin color in the absence of external environmental stimuli and those that develop irritative skin pigmentation, such as freckles and age spots (Non-Patent Documents 1, 2). Pigmentation levels vary significantly among races and individuals. To explore the genetic factors involved in skin pigmentation-related traits, studies have been conducted on many candidate genes, including BNC2, UGT1A8, IRF4, and POMC, in European and American populations (Non-Patent Documents 3, 4, 5). Furthermore, due to the genetic complexity of skin pigmentation-related traits, genome-wide association studies have been conducted to identify hundreds or even thousands of loci. Several genes, including MC1R, SLC24A5, SLC45A2, and BNC2, are known to be associated with skin pigmentation-related traits.

[0005] Most previous GWAS studies have focused on European populations, with few studies on Asian populations. Therefore, our understanding of genetic variants associated with skin pigmentation in Asian populations is limited, and further research on various populations is needed to discover new genetic variants and identify causal genes that regulate skin pigmentation. [Prior art documents] [Non-patent literature]

[0006] [Non-Patent Document 1] Shekar et al., J Invest Dermatol. 2005, 125: 1119-1129 [Non-patent document 2] Del Bino et al., Int J Mol Sci. 2018;19(9):2668 [Non-patent document 3] Jacobs et al., Hum Genet. 2013, 132: 147-158 [Non-patent document 4] Nan et al. al., Int J Cancer. 2009; 125: 909-917 [Non-Patent Document 5] Praetorius C et al., Cell. 2013; 155: 1022-1033 [Non-patent document 6] Wu and Wallace, Genomics 4, 560 (1989) [Non-Patent Document 7] Landegren et al., Science 241, 1077 (1988) [Non-patent document 8] Kwoh et al., Proc. Natl. Acad. Sci. USA 86, 1173 (1989) [Non-Patent Document 9] Guatelli et al., Proc. Natl. Acad. Sci. USA 87, 1874 (1990) Summary of the Invention [Problem to be solved by the invention]

[0007] The inventors of the present invention have identified the genetic characteristics that determine the skin characteristics of individuals, established scientific skin classification standards, discovered individually customized active ingredients based on these standards, and made earnest efforts to contribute to the development of customized cosmetics for each skin characteristic through detailed product subdivision. As a result, they have identified a method for diagnosing the presence or absence of pigmentation by selecting specific single nucleotide polymorphism (SNP) markers that have a significant correlation with skin pigmentation, and have completed the present invention. [Means for solving the problem]

[0008] An object of the present invention is to provide a single nucleotide polymorphism (SNP) marker for diagnosing the presence or absence of skin pigmentation.

[0009] Another object of the present invention is to provide a composition for diagnosing the presence or absence of skin pigmentation, which comprises a probe for detecting or an agent for amplifying a single nucleotide polymorphism (SNP) marker for diagnosing the presence or absence of skin pigmentation.

[0010] A further object of the present invention is to provide a kit or microarray for diagnosing the presence or absence of skin pigmentation, which comprises the composition for diagnosing the presence or absence of skin pigmentation.

[0011] A further object of the present invention is to provide a method for providing information relating to the presence or absence of skin pigmentation, which comprises the step of identifying the polymorphic site of the single nucleotide polymorphism marker. [Effects of the Invention]

[0012] The genetic polymorphism markers of the present invention having a significant association with the degree of skin pigmentation can provide information about the degree of skin pigmentation of an individual, and further, customized ingredients or products can be developed that can alleviate the degree of skin pigmentation depending on the information of the genetic polymorphism markers observed in an individual. DETAILED DESCRIPTION OF THE INVENTION

[0013] One aspect of the present invention provides single nucleotide polymorphism (SNP) markers for diagnosing the presence or absence of skin pigmentation.

[0014] Another aspect of the present invention provides a composition for diagnosing the presence or absence of skin pigmentation, comprising a probe for detecting or an agent for amplifying a single nucleotide polymorphism (SNP) marker for diagnosing the presence or absence of skin pigmentation.

[0015] Individuals are classified into skin types according to the presence or absence of skin pigmentation.

[0016] In the present invention, "polymorphism" refers to the presence of two or more alleles at a single locus, and a single nucleotide polymorphism (SNP) is a difference in a single nucleotide at a polymorphic site between individuals. A preferred polymorphic marker has two or more alleles that occur at a frequency of 1% or more, more specifically, 10% or 20% or more, in a selected population. A "genetic polymorphic marker" generally refers to a marker in which two or more alleles are observed at the same locus (base), and may generally be a major allele / major allele, a major allele / minor allele, or a minor allele / minor allele, depending on the individual. In the present invention, the term "polymorphic marker" is used interchangeably with "polymorphic marker" and refers to the base and base position of a minor allele, or is defined together with the chromosome number and base position, but is not limited thereto.

[0017] In the present invention, the term "allele" refers to a gene present at the same locus on a homologous chromosome and may refer to any genotype. The term "allele" is used to indicate polymorphism; for example, a SNP has two alleles. It also refers to a combination of two or more bases that have the same chromosomal number and base position, and these bases include a major allele that occurs frequently in individuals of a specific population, and a minor allele that occurs less frequently than the major allele.

[0018] Specifically, the genetic polymorphism marker of the present invention has a significant association with skin pigmentation, and when an individual has at least one minor allele among two alleles, it can be said that the skin pigmentation is significant compared to an individual having a major allele / major allele. That is, in the case of a major allele / minor allele or a minor allele / minor allele, it is known that the degree of skin pigmentation is higher or the skin characteristics are lower than in the case of a major allele / major allele.

[0019] In the present invention, "rs_id" refers to rs-ID, an independent index assigned to all SNPs initially registered by NCBI, which began accumulating SNP information in 1998. These rs_ids listed in the tables refer to SNP markers that are polymorphic markers of the present invention.

[0020] In the present invention, "skin type" refers to the skin type of an individual to be measured or diagnosed, and may be any skin type that can be measured by the SNP of the present invention, specifically pigmentation. The single nucleotide polymorphism marker of the present invention enables accurate measurement of skin type, and therefore can provide information on changes in skin type of skin exposed to active ingredients, and can provide personalized cosmetics, etc., but is not limited to these.

[0021] Since the skin pigmentation is also related to whitening, the skin diagnostic markers include, but are not limited to, markers for determining skin type, such as whether the skin is highly pigmented and easily tans or whether the skin is less pigmented and less susceptible to tanning.

[0022] For purposes of the present invention, the term "skin pigmentation" refers to the observation that a certain area of ​​an individual's skin has turned black or brown compared to the overall skin color, i.e., a portion of the skin that is relatively darker than the surrounding skin color, and refers to the result of measuring the proportion of areas that are black or brown. Reduction of pigmentation is associated with a skin whitening effect.

[0023] Specifically, the single nucleotide polymorphism marker is at least one type of single nucleotide polymorphism marker selected from the single nucleotide polymorphism markers shown in Tables 1 to 3. The single nucleotide polymorphism markers shown in Tables 1 to 3 may be used to determine whether or not they are associated with the degree of skin pigmentation.

[0024] The ability of the single nucleotide polymorphism markers of the present invention to diagnose skin type was determined by measuring the frequency of each marker. Such significance is characterized by a p-value such as, but not limited to, a p-value of less than 0.05, less than 0.01, less than 0.001, less than 0.0001, less than 0.00001, less than 0.000001, less than 0.0000001, less than 0.00000001, or less than 0.000000001. Specifically, a p-value of less than 0.01, more specifically a p-value of less than 0.001, and even more specifically, a p-value of less than 0.0001, but not limited to these.

[0025] The single nucleotide polymorphism (SNP) marker of the present invention is at least one selected from the markers shown in Tables 1 to 3, but is not limited to these. The single nucleotide polymorphism (SNP) marker is at least one, and is used in a combination of two or more, three or more, four or more, or any number of combinations that can determine pigmentation, but is not limited to these.

[0026] The marker is, but is not limited to, the SNP itself, a polynucleotide consisting of a continuous DNA sequence of 5 to 100 residues including the position of the SNP, or a polynucleotide consisting of a complementary sequence thereof.

[0027] As a specific example, the single nucleotide polymorphism marker is at least one selected from the markers shown in Table 1, but is not limited thereto.

[0028] Markers selected from the markers shown in Table 1 will be described below.

[0029] For example, if the SNP ID is rs1710447, the Chr.Position (GRCh ver.37) is described as "5:149192846," and the Allele is described as A>G, this indicates that the 149192846th base on human chromosome 5 is A or G, with the base to the left of the ">" in the allele representing the major allele and the base to the right representing the minor allele.

[0030] As a specific example, the markers selected from Table 1 include a polynucleotide comprising 5 to 100 consecutive DNA sequences including the 149192846th base of human chromosome 5, in which the 149192846th base is A or G (rs17110447), a polynucleotide comprising 5 to 100 consecutive DNA sequences including the 149192846th base of human chromosome 5, in which the 149191111th base of human chromosome 5 is C or T (rs4235745), and a polynucleotide comprising 5 to 100 consecutive DNA sequences including the 149191111th base of human chromosome 5, in which the 149195389th base of human chromosome 5 is T or a polynucleotide comprising 5 to 100 consecutive DNA sequences including the base at position 149196682 of human chromosome 5 where the base at position 149196682 is T or G (rs109077); and a polynucleotide comprising 5 to 100 consecutive DNA sequences including the base at position 149200603 of human chromosome 5 where the base at position 149200603 is T or C (rs32587). a polynucleotide comprising a sequence of 5 to 100 consecutive DNA residues including the 149194923 base and a polynucleotide comprising a sequence of 5 to 100 consecutive DNA residues including the 149194923 base and a polynucleotide comprising a sequence of 5 to 100 consecutive DNA residues including the 149202206 base and a polynucleotide comprising a sequence of 5 to 100 consecutive DNA residues including the 149202206 base and a polynucleotide comprising a sequence of 5 to 100 consecutive DNA residues including the 149202206 base and a polynucleotide comprising a sequence of 5 to 100 consecutive DNA residues including the 149202206 base and a polynucleotide comprising a sequence of 5 to 100 consecutive DNA residues including the 149202206 base and a polynucleotide comprising a sequence of 5 to 100 consecutive DNA residues including the 149194485 ... a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 149194485th base, a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 149195603rd base of human chromosome 5, in which the 149195603rd base is C or G (rs251466), and a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 149195603rd base of human chromosome 5, in which the 149196090th base is A or C (rs251465);a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 149196234 of human chromosome 5, in which the base at position 149196234 is G or C (rs251464); a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 149205630 of human chromosome 5, in which the base at position 149205630 is G or T (rs32581); and a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 149205630 of human chromosome 5, in which the base at position 149210848 is C or T (rs32579). a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the base at position 149211868 of human chromosome 5, in which the base at position 149211868 is G or A (rs32578); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the base at position 149211868 of human chromosome 5, in which the base at position 149209546 is C or T (rs32580); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the base at position 149209546 of human chromosome 5, in which the base at position 149212430 is G or A (rs32590); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149212430th base of human chromosome 5 in which the 149216304th base is A (rs45520937); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149216304th base of human chromosome 5 in which the 149216304th base is C or T (rs45543631); and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149226633rd base of human chromosome 5 in which the 149226633rd base is G or A (rs75739000). and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149216256th base and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149228648 ...a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149213456th base, and a polynucleotide in which the 149204852nd base of human chromosome 5 is C or G (rs17110586); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149204852nd base, and a polynucleotide in which the 149218886th base of human chromosome 5 is C or A (rs32574); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149218886th base, and a polynucleotide in which the 149218886th base of human chromosome 5 is C or A (rs32574). a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 149215213th base of human chromosome 5, in which the 149215213th base is C or G (rs32575); a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 149229822nd base of human chromosome 5, in which the 149229822nd base is G or T (rs6579761); a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 149229822nd base of human chromosome 5, in which the 149231519th base is C or T (rs26122); and a polynucleotide consisting of a contiguous DNA sequence of 5 to 100 bases including the 149233110 base on human chromosome 5 in which the base at position 149233110 is C or A (rs7712296); a polynucleotide consisting of a contiguous DNA sequence of 5 to 100 bases including the 149233110 base on human chromosome 5 in which the base at position 149233186 is C or T (rs17653703); and a polynucleotide consisting of a contiguous DNA sequence of 5 to 100 bases including the 149233186 base on human chromosome 5 in which the base at position 149216987 is A or G (rs a polynucleotide comprising 5 to 100 consecutive DNA sequences including the base at position 149199148 of human chromosome 5 (rs251459), in which the base at position 149199148 of human chromosome 5 is G or A; a polynucleotide comprising 5 to 100 consecutive DNA sequences including the base at position 149199148 of human chromosome 5 (rs26121), in which the base at position 149231830 of human chromosome 5 is A or G;A polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 149195125 of human chromosome 5, in which the base at position 149195125 is T or G (rs109076); a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 149232525 of human chromosome 5, in which the base at position 149232525 is A or G (rs888853); and a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 149197230 of human chromosome 5, in which the base at position 149197230 is T or C (rs251460). a polynucleotide comprising a 5 to 100 contiguous DNA sequence including the base at position 149232308 of human chromosome 5, wherein the base at position 149232308 is G or A (rs2341294); a polynucleotide comprising a 5 to 100 contiguous DNA sequence including the base at position 149232308 of human chromosome 5, wherein the base at position 149196329 of human chromosome 5 is G or A (rs251463); a polynucleotide comprising a 5 to 100 contiguous DNA sequence including the base at position 149196329 of human chromosome 5, wherein the base at position 149230952 of human chromosome 5 is G or A (rs251463). a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149230952 base in which the base is A or G (rs1549188); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149230745 base in human chromosome 5 in which the base is T or C (rs1549186); and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149230745 base in human chromosome 5 in which the base is C or T (rs1549187). and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149231786th base and a base in which the 149231786th base of human chromosome 5 is G or A (rs1107344); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149231786th base and a base in which the 149234235th base of human chromosome 5 is C or A (rs393499); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149234235th base and a base in which the 149234236th base of human chromosome 5 is A or T (rs439598);a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149234236th base, and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149159174th base of human chromosome 5 in which the 149159174th base is G or A (rs55926576); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149159174th base, and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149190810th base of human chromosome 5 in which the 149190810th base is C or T (rs79489540); a polynucleotide consisting of a 5-100 contiguous DNA sequence including a base at position 149194785 of human chromosome 5 in which the base is G or A (rs80069564); a polynucleotide consisting of a 5-100 contiguous DNA sequence including the base at position 149194785 of human chromosome 5 in which the base at position 149191547 of human chromosome 5 is C or T (rs78814834); a polynucleotide consisting of a 5-100 contiguous DNA sequence including the base at position 149191547 of human chromosome 5 in which the base at position 149193133 of human chromosome 5 is C or T (rs77655035) a polynucleotide comprising 5 to 100 consecutive DNA sequences including the 149193133rd base, and a polynucleotide comprising 5 to 100 consecutive DNA sequences including the 149195726th base of human chromosome 5 in which the 149195726th base is C or T (rs17110463), and a polynucleotide comprising 5 to 100 consecutive DNA sequences including the 149195726th base, and a polynucleotide comprising 5 to 100 consecutive DNA sequences including the 149196638th base of human chromosome 5 in which the 149196638th base is C or T (rs4705385). a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 149196916 of human chromosome 5, and a base at position 149196916 of human chromosome 5 being A or G (rs112183859); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 149196916 of human chromosome 5, and a base at position 149192166 of human chromosome 5 being T or C (rs4705384); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 149192166 of human chromosome 5, and a base at position 149197747 of human chromosome 5 being C or G (rs17600568);a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 149197747th base, and a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 149199467th base of human chromosome 5 in which the 149199467th base is C or T (rs79435714); a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 149199467th base, and a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 149197609th base of human chromosome 5 in which the 149197609th base is T or C (rs76390604); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 149197815 of human chromosome 5, in which the base at position 149197815 is T or C (rs10491360); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 149197815 of human chromosome 5, in which the base at position 149200932 is G or A (rs2003602); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 149200932 of human chromosome 5, in which the base at position 149190799 of human chromosome 5 is G or A (rs796 94606), a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149190799th base, and a polynucleotide in which the 149190248th base of human chromosome 5 is C or G (rs75548653), a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149190248th base, and a polynucleotide in which the 149203782nd base of human chromosome 5 is A or G (rs17653577), a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149203782nd base. a polynucleotide consisting of a nucleotide and a DNA sequence of 5 to 100 consecutive bases including the 149205992 base and a base in which the 149205992 base of human chromosome 5 is G or A (rs741582); a polynucleotide consisting of a nucleotide and a DNA sequence of 5 to 100 consecutive bases including the 149205992 base and a base in which the 149201956 base of human chromosome 5 is C or G (rs1078325); a polynucleotide consisting of a nucleotide and a DNA sequence of 5 to 100 consecutive bases including the 149201956 base and a base in which the 149208516 base of human chromosome 5 is G or T (rs76994147); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 149208516; a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 149206531 of human chromosome 5, in which the base at position 149206531 is G or A (rs45560442); and a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 149227540 of human chromosome 5, in which the base at position 149227540 is T or C (rs76174857);a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149204461st base of human chromosome 5, in which the 149204461st base is C or T (rs62382344); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149204461st base of human chromosome 5, in which the 149192744th base is G or T (rs67393352); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149192744th base of human chromosome 5, in which the 149189449th base is G or C (rs11948432); a polynucleotide consisting of a 5 to 100 contiguous DNA sequence including the 149205417th base and a polynucleotide consisting of a 5 to 100 contiguous DNA sequence including the 149205417th base and a polynucleotide consisting of a 5 to 100 contiguous DNA sequence including the 149205417th base and a polynucleotide consisting of a 5 to 100 contiguous DNA sequence including the 149196564th base and a polynucleotide consisting of a 5 to 100 contiguous DNA sequence including the 14920040 ...040th base and a polynucleotide consisting of a 5 to 100 contiguous DNA sequence including the 14920040th base and a polynucleotide consisting of a 5 to 100 contiguous DNA sequence including the 14920040th base and a polynucleotide consisting of a 5 to 100 contiguous DNA sequence including the 14920040th base and a polynucleotide consisting of a 5 to 100 contiguous DNA sequence including the 14920040th base and a polynucleotide consisting of a 5 to a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149200402nd base, in which the second base is A or G (rs17462080); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149199656th base of human chromosome 5, in which the 149199656th base is C or T (rs7729592); and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149199656th base of human chromosome 5, in which the 149196513th base is A or G (rs251462). a polynucleotide consisting of a NA sequence and the base at position 149199889 of human chromosome 5 being G or A (rs32589); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 149199889 and the base at position 149200920 of human chromosome 5 being A or G (rs32586); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 149200920 and the base at position 149202168 of human chromosome 5 being A or G (rs32585);a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 149202168th base, a polynucleotide in which the 149200043rd base of human chromosome 5 is T or C (rs32588), a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 149200043rd base, and a polynucleotide in which the 149203993rd base of human chromosome 5 is A or G (rs32584). a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 149187322 of human chromosome 5, in which the base at position 149187322 is G or A (rs73267734); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 149187322 of human chromosome 5, in which the base at position 149204444 of human chromosome 5 is C or T (rs32583); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 149204444 of human chromosome 5, in which the base at position 149178996 of human chromosome 5 is T or C (rs76861039); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 9178996th base, and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149179725th base of human chromosome 5 in which the 149179725th base is T or C (rs17461842); and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149185923th base of human chromosome 5 in which the 149185923rd base is C or A (rs75321435). and the base at position 149187212 of human chromosome 5 is C or T (rs80262653), a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 149187212, and the base at position 149187640 of human chromosome 5 is G or A (rs75294071), and a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 149187640, and the base at position 149183256 of human chromosome 5 is G or T (rs75465608),a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149183256th base, and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149234701th base of human chromosome 5 in which the 149234701th base is G or A (rs4705386), a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149234701th base, and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149236008th base of human chromosome 5 in which the 149236008th base is G or A (rs76295025), a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 149164366 of human chromosome 5, and a base at position 149230730 of human chromosome 5 that is G or A (rs74340302); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 149164366 of human chromosome 5, and a base at position 149230730 of human chromosome 5 that is C or T (rs25846); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 149230730 of human chromosome 5, and a base at position 149186478 of human chromosome 5 that is A or T (rs4705383); A polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149186478th base, and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149162451th base of human chromosome 5 in which the 149162451th base is G or A (rs62382308), and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149162451th base, and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149162294th base of human chromosome 5 in which the 149162294th base is G or A (rs72830233). a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 149212471 of human chromosome 5, wherein the base at position 149212471 is G or A (rs17572019); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 149212471 of human chromosome 5, wherein the base at position 149179741 is C or A (rs72830248); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 149179741 of human chromosome 5, wherein the base at position 149159862 is C or G (rs62382307);a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149159862nd base and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149184905th base of human chromosome 5 in which the 149184905th base is G or T (rs759814); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149184905th base and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 149159107th base of human chromosome 5 in which the 149159107th base is A or G (rs56160216); a polynucleotide comprising 5 to 100 consecutive DNA sequences including the 149211392nd base of a human chromosome in which the 149211392nd base is C or G (rs13178617); a polynucleotide comprising 5 to 100 consecutive DNA sequences including the 149211392nd base of a human chromosome in which the 149182832nd base is G or C (rs55650980); and a polynucleotide comprising 5 to 100 consecutive DNA sequences including the 149182832nd base of a human chromosome in which the 149208768th base is A or G (rs10491361). A polynucleotide consisting of 100 consecutive DNA sequences and a polynucleotide in which the base at position 16795790 on human chromosome 9 is A or C (rs16935073), a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the base at position 16795790 and a polynucleotide in which the base at position 16795241 on human chromosome 9 is T or C (rs10810635), a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the base at position 16795241 and a polynucleotide in which the base at position 16794418 on human chromosome 9 is C or A (rs10810635). a polynucleotide comprising 5 to 100 consecutive DNA sequences including the base at position 16806521 of human chromosome 9 (rs12376135), in which the base at position 16794418 is T or C (rs12351269), in which the base at position 16806521 of human chromosome 9 is T or C; and a polynucleotide comprising 5 to 100 consecutive DNA sequences including the base at position 16801450 of human chromosome 9 (rs4455968), in which the base at position 16801450 is G or T;a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 16808172nd base of human chromosome 9, in which the 16808172nd base is C or G (rs10122901); a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 16808172nd base of human chromosome 9, in which the 16806694th base of human chromosome 9 is G or C (rs10121347); a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 16806694th base of human chromosome 9, in which the 16801743rd base of human chromosome 9 is C or A (rs4523356); a polynucleotide consisting of a contiguous DNA sequence of 5 to 100 bases including the 16801120th base of human chromosome 9, in which the base at position 16801120 is A or C (rs10962609); a polynucleotide consisting of a contiguous DNA sequence of 5 to 100 bases including the 16801120th base of human chromosome 9, in which the base at position 16788274 is A or G (rs12378588); a polynucleotide consisting of a contiguous DNA sequence of 5 to 100 bases including the 16788274th base of human chromosome 9, in which the base at position 16788253 is T or C (rs12378588). a polynucleotide comprising 5 to 100 consecutive DNA sequences including the 16790074 base in human chromosome 9 where the 16790074 base is T or G (rs10115109); and a polynucleotide comprising 5 to 100 consecutive DNA sequences including the 16790074 base in human chromosome 9 where the 16790968 base is G or C (rs2183407). and a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 16788363 base and a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 16790960 ...9844 base and a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 16790960 base and a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 16790960 base and a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 16790960 base and a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 16790960 base and a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 16790960 base and a polynucleotide comprising a DNA sequence of 5 to 10 a polynucleotide comprising 5 to 100 consecutive DNA sequences including the 16799844th base, wherein the 16793202nd base of human chromosome 9 is T or C (rs12341168), a polynucleotide comprising 5 to 100 consecutive DNA sequences including the 16793202nd base, and a polynucleotide comprising 5 to 100 consecutive DNA sequences including the 16793104th base, wherein the 16793104th base of human chromosome 9 is A or G (rs10120562);a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 16792350 of human chromosome 9 (rs10119731), in which the base at position 16792350 is A or C; a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 16792350 of human chromosome 9 (rs10962601), in which the base at position 16796252 of human chromosome 9 is T or G; a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 16796252 of human chromosome 9 (rs10125996), in which the base at position 16792675 of human chromosome 9 is G or C; a polynucleotide comprising 5 to 100 contiguous DNA sequences including the base at position 16791865 of human chromosome 9, where the base at position 16791865 is C or T (rs12380481); a polynucleotide comprising 5 to 100 contiguous DNA sequences including the base at position 16791865 of human chromosome 9, where the base at position 16787767 of human chromosome 9 is T or C (rs73410488); a polynucleotide comprising 5 to 100 contiguous DNA sequences including the base at position 16787767 of human chromosome 9, where the base at position 16788327 of human chromosome 9 is T or C (rs73410488). a polynucleotide comprising a 5 to 100 contiguous DNA sequence including the 16788327th base of human chromosome 9, where the base is A or G (rs10756814); a polynucleotide comprising a 5 to 100 contiguous DNA sequence including the 16788333th base of human chromosome 9, where the base is T or C (rs74645810); and a polynucleotide comprising a 5 to 100 contiguous DNA sequence including the 16788336th base of human chromosome 9, where the base is A or G (rs76233908). a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the 16788308 base and a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the 1678832 ...A polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 16815861 base and a polynucleotide in which the 16825110 base of human chromosome 9 is C or T (rs7043062), a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 16825110 base and a polynucleotide in which the 16789652 base of human chromosome 9 is T or C (rs4961496), a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 16789652 base and a polynucleotide in which the 16789652 base of human chromosome 9 is T or C (rs4961496). a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 16795159th base (rs10962598), where the 6795159th base is A or G; a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 16812810th base (rs10962618), where the 16812810th base of human chromosome 9 is T or C; and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 16789024th base (rs10810632), where the 16789024th base of human chromosome 9 is T or C. a polynucleotide consisting of a continuous DNA sequence containing 5 to 100 bases including the 16789436th base and a polynucleotide consisting of a continuous DNA sequence containing 5 to 100 bases including the 16789436th base and a polynucleotide consisting of a continuous DNA sequence containing 5 to 100 bases including the 16820923 ... a polynucleotide comprising 5 to 100 consecutive DNA sequences including the base at position 16795588 of human chromosome 9 (rs57542309), in which the base at position 16795211 of human chromosome 9 is G or C; and a polynucleotide comprising 5 to 100 consecutive DNA sequences including the base at position 16824921 of human chromosome 9 (rs10810640), in which the base at position 16824921 of human chromosome 9 is C or G.A polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 16788367th base of human chromosome 9 (rs10810631), in which the 16788367th base is C or T; a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 16788367th base of human chromosome 9 (rs17096846), in which the 119568133rd base of human chromosome 10 is G or A (rs17096846), in which the 119568133rd base of human chromosome 10 is A or T (rs1925258), in which the 119 a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 570121st base, and a polynucleotide in which the 119569921st base of human chromosome 10 is G or A (rs1925257), a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119569921st base, and a polynucleotide in which the 119570915th base of human chromosome 10 is G or T (rs55927713), a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119570915th base, and a polynucleotide in which the 119570915th base of human chromosome 10 is G or T (rs55927713), a polynucleotide consisting of a continuous DNA sequence of 5 to 100 bases including the base at position 119571832 of human chromosome 10, in which the base at position 119571832 is G or A (rs17096850); a polynucleotide consisting of a continuous DNA sequence of 5 to 100 bases including the base at position 119572168 of human chromosome 10, in which the base at position 119572168 is C or A (rs4751640); a polynucleotide consisting of a continuous DNA sequence of 5 to 100 bases including the base at position 119572168 of human chromosome 10, in which the base at position 119547342 is C or T (rs4752110); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 547342nd base; a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119561946th base in human chromosome 10, in which the 119561946th base is C or T (rs61865966); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119570716th base in human chromosome 10, in which the 119570716th base is C or A (rs28605039);a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 119563422 of human chromosome 10, in which the base at position 119563422 is T or A (rs61865967); a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 119563422 of human chromosome 10, in which the base at position 119544822 is A or G (rs7098480); a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 119544822 of human chromosome 10, in which the base at position 119544385 is C or T (rs9804204); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 9544385th base, a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119547279th base of human chromosome 10 in which the 119547279th base is G or T (rs2025562), a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119547279th base, and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119544027th base of human chromosome 10 in which the 119544027th base is G or T (rs10749248), a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 119545571 of human chromosome 10, in which the base at position 119545571 is G or A (rs10749249); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 119547081 of human chromosome 10, in which the base at position 119547081 is T or C (rs10749250); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 119547081 of human chromosome 10, in which the base at position 119547669 is A or G (rs72829865); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the 19547669th base, a polynucleotide in which the 119545287th base of human chromosome 10 is T or G (rs7099175), a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the 119545287th base, and a polynucleotide in which the 119545401st base of human chromosome 10 is G or A (rs10787792), a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the 119545401st basea polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 119545101st base of human chromosome 10, where the 119545101st base is T or C (rs1925285); a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 119545375th base of human chromosome 10, where the 119545375th base is A or T (rs10787791); and a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 119545375th base of human chromosome 10, where the 119545741st base is T or G (rs4752106). a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119545762 base and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119545762 base and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119546979 base and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119546979 base and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119546979 base and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119545238 base and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119545238 base and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119545762 base and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119546979 base and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119545238 base and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119545762 ... or C (rs7098850), a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119545238th base of human chromosome 10; a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119546034th base of human chromosome 10; a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119546034th base of human chromosome 10; and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119546496th base of human chromosome 10; a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119546496th base of human chromosome 10; and a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 119546323 base and a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 119546323 base and a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 119552651 base and a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 119552651 base and a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 119552651 base and a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 119552651 base and a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 119566093 ...52651 base and a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 119552651 4) a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119566093rd base, and a polynucleotide in which the 119564143rd base of human chromosome 10 is C or T (rs11198112), a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119564143rd base, and a polynucleotide in which the 119563401st base of human chromosome 10 is T or C (rs10444110), a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119563401st base,a polynucleotide consisting of a continuous DNA sequence of 5 to 100 bases including the base at position 119565538 of human chromosome 10 (rs10444039), a polynucleotide consisting of a continuous DNA sequence of 5 to 100 bases including the base at position 119565538; a polynucleotide consisting of a continuous DNA sequence of 5 to 100 bases including the base at position 119561969 of human chromosome 10 (rs7070575), a polynucleotide consisting of a continuous DNA sequence of 5 to 100 bases including the base at position 119561969; and a polynucleotide consisting of a continuous DNA sequence of 5 to 100 bases including the base at position 119573178 of human chromosome 10 (rs7098111), a polynucleotide consisting of a continuous DNA sequence of 5 to 100 bases including the base at position 119561969 of human chromosome 10 (rs7098111). a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 573178th base, a polynucleotide in which the 119572403rd base of human chromosome 10 is C or T (rs35563099), a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119572403rd base, a polynucleotide in which the 119587425th base of human chromosome 10 is G or A (rs4751641), a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119587425th base, and a polynucleotide in which the 119587425th base of human chromosome 10 is G or A (rs4751641), a polynucleotide consisting of a 5 to 100 contiguous DNA sequence including the 119584730th base of human chromosome 10 (rs61865972), in which the 119584730th base of human chromosome 10 is C or T; a polynucleotide consisting of a 5 to 100 contiguous DNA sequence including the 119599727th base of human chromosome 10 (rs61866015), in which the 119599727th base of human chromosome 10 is A or G; a polynucleotide consisting of a 5 to 100 contiguous DNA sequence including the 119599727th base of human chromosome 10 (rs1806957), in which the 1195 a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the 75974th base, a polynucleotide in which the 119576317th base of human chromosome 10 is G or C (rs555269109), a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the 119576317th base, and a polynucleotide in which the 119576318th base of human chromosome 10 is G or T (rs532411111);A polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 119576319th base of human chromosome 10, in which the 119576319th base is C or G (rs4994045); a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 119576319th base of human chromosome 10, in which the 119584861st base is A or G (rs6585463); a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 119584861st base of human chromosome 10, in which the 119562387th base of human chromosome 10 is C or T (rs12146158); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 9562387th base, a polynucleotide in which the 119572476th base of human chromosome 10 is C or A (rs74317863), a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119572476th base, and a polynucleotide in which the 119577677th base of human chromosome 10 is G or A (rs34878973), a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 119577677th base a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 119601436 of human chromosome 10, in which the base at position 119601436 is T or G (rs7098136); a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 119601436 of human chromosome 10, in which the base at position 119575798 of human chromosome 10 is C or T (rs12773211); a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 119575798 of human chromosome 10, in which the base at position 119601939 of human chromosome 10 is G or C (rs7916406); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the 9601939th base; a polynucleotide in which the 119602316th base of human chromosome 10 is G or A (rs61866016), a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the 119602316th base; and a polynucleotide in which the 119602424th base of human chromosome 10 is G or T (rs61866017), a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the 119602424th base.a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 119601743rd base of human chromosome 10, in which the 119601743rd base is G or A (rs12250372); a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 119601743rd base of human chromosome 10, in which the 119586963rd base is C or T (rs4752118); a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the 119586963rd base of human chromosome 10, in which the 119586186th base is A or T (rs10749252); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the 19586186th base; a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the 119586231st base of human chromosome 10, in which the 119586231st base is C or T (rs7085292); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the 119586178th base of human chromosome 10, in which the 119586178th base is C or T (rs4752117); a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 119587158 of human chromosome 10 (rs10749253), a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 119587158; a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 119591330 of human chromosome 10 (rs10886151), a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 119591330 of human chromosome 10 (rs4752119 ... and a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 119591330 of human chromosome 10 (rs4752119). a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the 19586980th base, a polynucleotide in which the 119586462nd base of human chromosome 10 is C or A (rs4431946), a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the 119586462nd base, and a polynucleotide in which the 119592083rd base of human chromosome 10 is C or T (rs1925264), a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the 119592083rd basea polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 119595140 of human chromosome 10 (rs11498896), in which the base at position 119595140 is G or A; a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 119595140 of human chromosome 10 (rs4752116), in which the base at position 119582802 of human chromosome 10 is C or T; a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 119582802 of human chromosome 10 (rs4752116), in which the base at position 119591168 of human chromosome 10 is C or A (rs11198135), in which the base at position 11959116 a polynucleotide consisting of a 5 to 100 contiguous DNA sequence including the 8th base, and a polynucleotide in which the 119581527th base of human chromosome 10 is G or A (rs10886148); a polynucleotide consisting of a 5 to 100 contiguous DNA sequence including the 119581527th base, and a polynucleotide in which the 89985940th base of human chromosome 16 is G or A (rs2228479); a polynucleotide consisting of a 5 to 100 contiguous DNA sequence including the 89985940th base, and a polynucleotide in which the 899867th base of human chromosome 16 is G or A (rs2228479); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 89986760th base, in which the 60th base is A or G (rs3212369); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 89987201st base of human chromosome 16, in which the 89987201st base is A or G (rs3212371); and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 89987201st base, in which the 89986608th base of human chromosome 16 is A or G (rs2228478). and the base at position 89985177 of human chromosome 16 is T or C (rs3212359); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 89985177 and the base at position 89985441 of human chromosome 16 is T or A (rs3212363); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 89985441 and the base at position 89986025 of human chromosome 16 is T or C (rs33932559);a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 89986025th base, and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 89986154th base in human chromosome 16 where the 89986154th base is A or G (rs885479), and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 89986154th base, and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 89985222nd base in human chromosome 16 where the 89985222nd base is A or G (rs3212361); a polynucleotide comprising a nucleotide sequence of 5 to 100 consecutive bases including the base at position 200473658 of human chromosome 2, a polynucleotide comprising a nucleotide sequence of 5 to 100 consecutive bases including the base at position 200473658 of human chromosome 2, a polynucleotide comprising a nucleotide sequence of 5 to 100 consecutive bases including the base at position 200475044 of human chromosome 2, and a polynucleotide comprising a nucleotide sequence of 5 to 100 consecutive bases including the base at position 200475044 of human chromosome 2, and a polynucleotide comprising a nucleotide sequence of 5 to 100 consecutive bases including the base at position 200475044 of human chromosome 2, and a polynucleotide comprising a nucleotide sequence of 5 to 100 consecutive bases including the base at position 200475044 of human chromosome 2, and a polynucleotide comprising a nucleotide sequence of 5 to 100 consecutive bases including the base at position 200492565 of human chromosome 2, and a polynucleotide comprising a nucleotide sequence of 5 to 100 consecutive bases including the base at position 200492565 of human chromosome 2, and a polynucleotide comprising a nucleotide sequence of 5 to 100 consecutive bases including the base at position 20047504 ... a polynucleotide comprising a contiguous DNA sequence of 5 to 100 bases including the base at position 200492565; a polynucleotide comprising a contiguous DNA sequence of 5 to 100 bases including the base at position 200492076 of human chromosome 2 in which the base at position 200492076 is A or C (rs4673381); and a polynucleotide comprising a contiguous DNA sequence of 5 to 100 bases including the base at position 200484107 of human chromosome 2 in which the base at position 200484107 is A or G (rs1823487). a polynucleotide consisting of a 5 to 100 contiguous DNA sequence including the base at position 200478921 of human chromosome 2, in which the base at position 200478921 is T or G (rs1450566); a polynucleotide consisting of a 5 to 100 contiguous DNA sequence including the base at position 200491198 of human chromosome 2, in which the base at position 200491198 is G or C (rs62180586); a polynucleotide consisting of a 5 to 100 contiguous DNA sequence including the base at position 200491299 of human chromosome 2, in which the base at position 200491299 is G or A (rs13419888); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 00491299; a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 200477380 of human chromosome 2, in which the base at position 200477380 is A or T (rs1450571); and a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 200477504 of human chromosome 2, in which the base at position 200477504 is C or T (rs10563018);a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 200477506 of human chromosome 2, in which the base at position 200477506 is A or C (rs56112313); a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 200484696 of human chromosome 2, in which the base at position 200484696 is A or G (rs2034486); and a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 200485100 of human chromosome 2, in which the base at position 200485100 is T or C (rs7591758). a polynucleotide consisting of 5 to 100 consecutive DNA sequences containing the base at position 200487486 of human chromosome 2, in which the base at position 200487486 is C or A (rs1868723); a polynucleotide consisting of 5 to 100 consecutive DNA sequences containing the base at position 200487486 of human chromosome 2, in which the base at position 200491726 is A or C (rs7597643); a polynucleotide consisting of 5 to 100 consecutive DNA sequences containing the base at position 200491726 of human chromosome 2, in which the base at position 200491877 of human chromosome 2 is A or C (rs7597643). a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the base at position 200491877 of human chromosome 2 in which the base is A or G (rs4675732); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the base at position 200484452 of human chromosome 2 in which the base is T or G (rs2034484); and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the base at position 200491187 of human chromosome 2 in which the base is A or G (rs13394614). a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the 200479539 base and a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the 200479539 base and a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the 200488306 base and a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the 200488306 base and a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the 200488306 base and a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the 200488306 base and a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the 200488785 ...785 base and a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the 200488306 base and a polynucleotide consisting of a DNA sequence of 5 to 100a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 200488785th base, and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 200488905th base of human chromosome 2 in which the 200488905th base is A or G (rs1450564), and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 200488905th base, and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 200489109th base of human chromosome 2 in which the 200489109th base is G or A (rs1450563). a polynucleotide consisting of a 5 to 100 contiguous DNA sequence including a base at position 200484657 of human chromosome 2 and a base at position 200481019 of human chromosome 2 being C or G (rs2167215); a polynucleotide consisting of a 5 to 100 contiguous DNA sequence including a base at position 200481019 of human chromosome 2 being A or T (rs1376134); a polynucleotide consisting of a 5 to 100 contiguous DNA sequence including a base at position 200481019 of human chromosome 2 and a base at position 200486976 of human chromosome 2 being T or G (rs983677); a polynucleotide comprising a 5 to 100 contiguous DNA sequence including the 200486976th base, and a polynucleotide comprising a 5 to 100 contiguous DNA sequence including the 200487539th base of human chromosome 2 in which the 200487539th base is G or C (rs1868724); a polynucleotide comprising a 5 to 100 contiguous DNA sequence including the 200487539th base, and a polynucleotide comprising a 5 to 100 contiguous DNA sequence including the 200489964th base of human chromosome 2 in which the 200489964th base is C or G (rs10206526); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 200490260 of human chromosome 2 and a base at position 200491038 of human chromosome 2 being A or G (rs12467197); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 200491038 of human chromosome 2 and a base at position 200482025 of human chromosome 2 being A or G (rs6730854);a polynucleotide comprising a 5 to 100 contiguous DNA sequence including the 200482025th base, and a polynucleotide comprising a 5 to 100 contiguous DNA sequence including the 200482231th base of human chromosome 2 in which the 200482231th base is G or A (rs6759297), and a polynucleotide comprising a 5 to 100 contiguous DNA sequence including the 200482231th base, and a polynucleotide comprising a 5 to 100 contiguous DNA sequence including the 200482513th base of human chromosome 2 in which the 200482513th base is C or T (rs1450567). a polynucleotide consisting of a 5 to 100 contiguous DNA sequence including the base at position 200480777 of human chromosome 2, in which the base at position 200480777 is T or C (rs1376133), a polynucleotide consisting of a 5 to 100 contiguous DNA sequence including the base at position 200481498 of human chromosome 2, in which the base at position 200481498 is C or G (rs2122532), a polynucleotide consisting of a 5 to 100 contiguous DNA sequence including the base at position 200481498 of human chromosome 2, in which the base at position 200481506 is A or T (rs2122533), a polynucleotide comprising a 5 to 100 contiguous DNA sequence including the 200481506 base, and a polynucleotide comprising a 5 to 100 contiguous DNA sequence including the 200495743 base in human chromosome 2 where the 200495743 base is A or C (rs4675733), and a polynucleotide comprising a 5 to 100 contiguous DNA sequence including the 200495743 base in human chromosome 2 where the 200482881 base is A or T (rs4507037). a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 200499444 of human chromosome 2, in which the base at position 200499444 is G or A (rs12693894); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 200499255 of human chromosome 2, in which the base at position 200499255 is T or A (rs12052634); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 200499255 of human chromosome 2, in which the base at position 200491272 is A or G (rs13394647);a polynucleotide comprising a 5 to 100 contiguous DNA sequence including the 200491272nd base, a polynucleotide comprising a 5 to 100 contiguous DNA sequence including the 200474888th base of human chromosome 2 in which the 200474888th base is C or A (rs768637), a polynucleotide comprising a 5 to 100 contiguous DNA sequence including the 200474888th base, and a polynucleotide comprising a 5 to 100 contiguous DNA sequence including the 200478354th base of human chromosome 2 in which the 200478354th base is G or C (rs4675720). a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 200484686 of human chromosome 2, in which the base at position 200484686 is C or T (rs2034485); a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 200485648 of human chromosome 2, in which the base at position 200485648 is T or C (rs6743286); a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 200485648 of human chromosome 2, in which the base at position 200498327 is C or T (rs78394027); a polynucleotide comprising a 5 to 100 contiguous DNA sequence including the 200498327th base, and a polynucleotide comprising a 5 to 100 contiguous DNA sequence including the 200501964th base of human chromosome 2 in which the 200501964th base is C or G (rs7562843); a polynucleotide comprising a 5 to 100 contiguous DNA sequence including the 200499206th base of human chromosome 2 in which the 200499206th base is C or G (rs12053334); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including a base at position 200500431 of human chromosome 2 in which the base is C or T (rs4624324); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 200500431 of human chromosome 2 in which the base is T or C (rs12477506); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 200500296 of human chromosome 2 in which the base at position 2005006846 of human chromosome 2 in which the base is C or T (rs28890501);a polynucleotide consisting of 5 to 100 contiguous DNA sequences including the 200506846th base and a polynucleotide in which the 200492529th base of human chromosome 2 is A or C (rs1901151); a polynucleotide consisting of 5 to 100 contiguous DNA sequences including the 200492529th base and a polynucleotide in which the 200501467th base of human chromosome 2 is T or A (rs57791827); a polynucleotide consisting of 5 to 100 contiguous DNA sequences including the 200501467th base and a polynucleotide in which the 200505203rd base of human chromosome 2 is T or G (rs4673384); A polynucleotide consisting of a continuous DNA sequence, and the base at position 200494912 of human chromosome 2 is A or G (rs7609357); a polynucleotide consisting of 5 to 100 continuous DNA sequences including the base at position 200494912, and the base at position 200496036 of human chromosome 2 is T or C (rs4673383); a polynucleotide consisting of 5 to 100 continuous DNA sequences including the base at position 200496036, and the base at position 200497907 of human chromosome 2 is T or G. a polynucleotide comprising 5 to 100 consecutive DNA sequences including the base at position 200499399 of human chromosome 2 (rs1450561), a polynucleotide comprising 5 to 100 consecutive DNA sequences including the base at position 200499399 of human chromosome 2 in which the base at position 200499399 is A or G (rs11691837), and a polynucleotide comprising 5 to 100 consecutive DNA sequences including the base at position 200499399 of human chromosome 2 in which the base at position 200501134 is T or C (rs10191530). a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 200499157 of human chromosome 2 and a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 200499157 of human chromosome 2 and a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 200498080 of human chromosome 2 and a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 200498080 of human chromosome 2 and a polynucleotide comprising a DNA sequence of 5 to 100 consecutive bases including the base at position 200490231 ... 4) a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 200490231, and a polynucleotide in which the base at position 200497975 of human chromosome 2 is G or A (rs1450560), a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 200497975, and a polynucleotide in which the base at position 200501827 of human chromosome 2 is T or C (rs10194512), and a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 200501827;A polynucleotide comprising a 5 to 100 contiguous DNA sequence containing the 200489315th base of human chromosome 2, in which the 200489315th base is G or A (rs17590093); a polynucleotide comprising a 5 to 100 contiguous DNA sequence containing the 200497286th base of human chromosome 2, in which the 200497286th base is G or T (rs7578193); and a polynucleotide comprising a 5 to 100 contiguous DNA sequence containing the 200497286th base of human chromosome 2, in which the 200494182nd base is G or A (rs1450562). and a polynucleotide comprising 5 to 100 consecutive DNA sequences including the base at position 200497711 of human chromosome 2, wherein the base at position 200497711 of human chromosome 2 is A or G (rs4675735), a polynucleotide comprising 5 to 100 consecutive DNA sequences including the base at position 200497711 of human chromosome 2, wherein the base at position 200496814 of human chromosome 2 is A or T (rs4675734), a polynucleotide comprising 5 to 100 consecutive DNA sequences including the base at position 200496814 of human chromosome 2, wherein the base at position 200509555 of human chromosome 2 is A or T (rs4675734). a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 200509555 base at position 200509556 of human chromosome 2 in which the 200509556 base is G or A (rs149819797); a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 200509556 base at position 200509556 of human chromosome 2 in which the 200509556 base is C or T (rs145839112); and a polynucleotide consisting of 5 to 100 consecutive DNA sequences including the 200495510 base at position 200495510 of human chromosome 2 in which the 200495510 base is A or G (rs77833142). and a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 200510641 of human chromosome 2, in which the base at position 200510641 is A or C (rs78251380); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 200510641 of human chromosome 2, in which the base at position 200510941 is T or G (rs80333946); a polynucleotide consisting of a DNA sequence of 5 to 100 consecutive bases including the base at position 200510941 of human chromosome 19, in which the base at position 3548231 is A or G (rs2240751);The markers comprise at least one polynucleotide selected from the group consisting of a polynucleotide consisting of 5 to 100 contiguous DNA sequences including the base at position 3548231, a polynucleotide consisting of 5 to 100 contiguous DNA sequences including the base at position 3542983 of human chromosome 19 where the base at position 3542983 is C or T (rs12608592), a polynucleotide consisting of 5 to 100 contiguous DNA sequences including the base at position 3542983 where the base at position 3540539 of human chromosome 19 is G or C (rs12984831), and complementary polynucleotides thereof, but are not limited to the above examples. The markers are only a partial list of examples shown in Table 1, and may be selected in a similar manner for chromosomes at other positions.

[0031] As another specific example, similar to Table 1, at least one single nucleotide polymorphism (SNP) marker is selected from those shown in Table 2, but is not limited thereto.

[0032] As another specific example, similar to Table 1, at least one single nucleotide polymorphism (SNP) marker is selected from those shown in Table 3, but is not limited thereto.

[0033] The single nucleotide polymorphism markers shown in Tables 2 and 3 are analyzed and selected as described above, but are not limited to these.

[0034] The alleles of the present invention have the same number on a chromosome in each individual, and include major and minor alleles of SNPs. As the minor allele of a base at a polymorphic site of a polymorphic marker increases by one, the major allele decreases by one, and as the major allele increases by one, the minor allele decreases by one. However, the range in which the minor and major alleles increase or decrease falls within three types: i) major allele / major allele, ii) major allele / minor allele, and iii) minor allele / minor allele. The alleles increase or decrease within these three types, but are not limited thereto.

[0035] Furthermore, the markers of the present invention are markers that can determine the degree of increase or decrease in phenotype (pigmentation) in response to an increase in the major allele of the base at the polymorphic site of the polymorphic marker in an individual. For example, among the markers shown in Table 1, when the base at position 149192846 on chromosome 5 of an individual is the minor allele A (rs17110447), the effect size is negative (-), and therefore pigmentation is determined to decrease. When the base at position 16795241 on chromosome 9 of an individual is the minor allele C (rs10810635), the effect size is positive (+), and therefore pigmentation is determined to increase, but the present invention is not limited to these.

[0036] Specifically, the single nucleotide polymorphism marker increases pigmentation when it contains at least one of the following bases, which are major alleles, but is not limited to these. The 16795790th base of human chromosome 9 is A The 16795241st base of human chromosome 9 is T The 16794418th base of human chromosome 9 is C The 16806521st base of human chromosome 9 is T The base at position 16801450 on human chromosome 9 is G The 16808172nd base of human chromosome 9 is C The 16806694th base of human chromosome 9 is G The 16801743rd base of human chromosome 9 is C The base at position 16801120 of human chromosome 9 is A The 16788274th base of human chromosome 9 is A The 16788253rd base of human chromosome 9 is T The 16790074th base of human chromosome 9 is T The 16790968th base of human chromosome 9 is G The 16788363rd base of human chromosome 9 is A The 16790960th base of human chromosome 9 is A The 16799844th base of human chromosome 9 is C The 16793202nd base of human chromosome 9 is T The 16793104th base of human chromosome 9 is A The 16792350th base of human chromosome 9 is A The 16796252nd base of human chromosome 9 is T The 16792675th base of human chromosome 9 is G The 16791865th base of human chromosome 9 is C The 16787767th base of human chromosome 9 is T The 119568133rd base of human chromosome 10 is G The 119570121st base of human chromosome 10 is A The 119569921st base of human chromosome 10 is G The 119570915th base of human chromosome 10 is G The 119571832nd base of human chromosome 10 is G The 119572168th base of human chromosome 10 is C The 119547342nd base of human chromosome 10 is C The 119561946th base of human chromosome 10 is C The 119570716th base of human chromosome 10 is C The 119563422nd base of human chromosome 10 is T The 119544822nd base of human chromosome 10 is A The 119544385th base of human chromosome 10 is C The 119547279th base of human chromosome 10 is G The 119544027th base of human chromosome 10 is G The 119545571st base of human chromosome 10 is G The 119547081st base of human chromosome 10 is T The 119547669th base of human chromosome 10 is A The 119545287th base of human chromosome 10 is T The 119545401st base of human chromosome 10 is G The 119545101st base of human chromosome 10 is T The 119545375th base of human chromosome 10 is A The 119545741st base of human chromosome 10 is T The 119545762nd base of human chromosome 10 is T The 119546979th base of human chromosome 10 is T The 119545238th base of human chromosome 10 is T The 119546034th base of human chromosome 10 is A The 119546496th base of human chromosome 10 is G The 119546323rd base of human chromosome 10 is A The 119552651st base of human chromosome 10 is G The 119566093rd base of human chromosome 10 is C The base at position 89985940 on human chromosome 16 is G The 89986760th base of human chromosome 16 is A The 89987201st base of human chromosome 16 is A The 89986608th base of human chromosome 16 is A The 89985177th base of human chromosome 16 is T The 89985441st base of human chromosome 16 is T The 89986025th base of human chromosome 16 is T The 89986154th base of human chromosome 16 is A The 89985222nd base of human chromosome 16 is A The 200473658th base of human chromosome 2 is C The 200475044th base of human chromosome 2 is C The 200492565th base of human chromosome 2 is A The 200492076th base of human chromosome 2 is A The 200484107th base of human chromosome 2 is A The 200478921st base of human chromosome 2 is T The 200491198th base of human chromosome 2 is G The 200491299th base of human chromosome 2 is G The 200477380th base of human chromosome 2 is A The 200477504th base of human chromosome 2 is C The 200477506th base of human chromosome 2 is A The 200484696th base of human chromosome 2 is A The 200485100th base of human chromosome 2 is T The 200487486th base of human chromosome 2 is C The 200491726th base of human chromosome 2 is A The 200491877th base of human chromosome 2 is A The 200484452nd base of human chromosome 2 is T The 200491187th base of human chromosome 2 is A The 200479539th base of human chromosome 2 is A The 200488306th base of human chromosome 2 is T The 200488785th base of human chromosome 2 is T The 200488905th base of human chromosome 2 is A The 200489109th base of human chromosome 2 is G The 200484657th base of human chromosome 2 is C The 200481019th base of human chromosome 2 is A The 200486976th base of human chromosome 2 is T The 200487539th base of human chromosome 2 is G The 200489964th base of human chromosome 2 is C The 200490260th base of human chromosome 2 is A The 200491038th base of human chromosome 2 is A The 200482025th base of human chromosome 2 is A The 200482231st base of human chromosome 2 is G The 200482513th base of human chromosome 2 is C The 200480777th base of human chromosome 2 is T The 200481498th base of human chromosome 2 is C The 200481506th base of human chromosome 2 is A The 200495743rd base of human chromosome 2 is A The 200482881st base of human chromosome 2 is A The 200499444th base of human chromosome 2 is G The 200499255th base of human chromosome 2 is T The 200491272nd base of human chromosome 2 is A The 200474888th base of human chromosome 2 is C The 200478354th base of human chromosome 2 is G The 200484686th base of human chromosome 2 is C The 200485648th base of human chromosome 2 is T The 200498327th base of human chromosome 2 is C The 200501964th base of human chromosome 2 is C The 200499206th base of human chromosome 2 is C The 200500431st base of human chromosome 2 is C The 200500296th base of human chromosome 2 is T The 200506846th base of human chromosome 2 is C The 200492529th base of human chromosome 2 is A The 200501467th base of human chromosome 2 is T The 200505203 base of human chromosome 2 is T The 200494912th base of human chromosome 2 is A The 200496036th base of human chromosome 2 is T The 200497907th base of human chromosome 2 is T The 200499399th base of human chromosome 2 is A The 200501134th base of human chromosome 2 is T The 200499157th base of human chromosome 2 is A The 200498080th base of human chromosome 2 is A The 200490231st base of human chromosome 2 is C The 200497975th base of human chromosome 2 is G The 200501827th base of human chromosome 2 is T The 200489315th base of human chromosome 2 is G The 200497286th base of human chromosome 2 is G The 200494182nd base of human chromosome 2 is G The 200497711th base of human chromosome 2 is A The 200496814th base of human chromosome 2 is A The 200509555th base of human chromosome 2 is G The 200509556th base of human chromosome 2 is C The 200495510th base of human chromosome 2 is A The 200510641st base of human chromosome 2 is A The 200510941st base of human chromosome 2 is T

[0037] Furthermore, the single nucleotide polymorphism marker reduces pigmentation when it contains at least one of the following bases, which are major alleles, but is not limited thereto.

[0038] The 149192846th base of human chromosome 5 is A The 149191111th base of human chromosome 5 is C The 149195389th base of human chromosome 5 is T The 149196682nd base of human chromosome 5 is T The 149200603 base of human chromosome 5 is T The 149194923 base of human chromosome 5 is T The 149202206th base of human chromosome 5 is C The 149194485th base of human chromosome 5 is C The 149195603 base of human chromosome 5 is C The 149196090th base of human chromosome 5 is A The 149196234th base of human chromosome 5 is G The base at position 149205630 of human chromosome 5 is G The 149210848th base of human chromosome 5 is C The 149211868th base of human chromosome 5 is G The 149209546th base of human chromosome 5 is C The base at position 149212430 of human chromosome 5 is G The 149216304th base of human chromosome 5 is C The 149226633rd base of human chromosome 5 is G The 149216256th base of human chromosome 5 is C The 149228648th base of human chromosome 5 is C The 149213456th base of human chromosome 5 is A The 149204852nd base of human chromosome 5 is C The 149218886th base of human chromosome 5 is C The 149215213th base of human chromosome 5 is C The 149229822nd base of human chromosome 5 is G The 149231519th base of human chromosome 5 is C The 149233110th base of human chromosome 5 is C The 149233186th base of human chromosome 5 is C The 149216987th base of human chromosome 5 is A The 149199148th base of human chromosome 5 is G The base at position 149231830 of human chromosome 5 is A The 149195125th base of human chromosome 5 is T The 149232525th base of human chromosome 5 is A The base at position 149197230 of human chromosome 5 is T The 149232308th base of human chromosome 5 is G The 149196329th base of human chromosome 5 is G The 149230952nd base of human chromosome 5 is A The base at position 149230745 of human chromosome 5 is T The 149230787th base of human chromosome 5 is C The 149231786th base of human chromosome 5 is G The 149234235th base of human chromosome 5 is C The 149234236th base of human chromosome 5 is A The 149159174th base of human chromosome 5 is G The 149190810th base of human chromosome 5 is C The 149194785th base of human chromosome 5 is G The 149191547th base of human chromosome 5 is C The 149193133rd base of human chromosome 5 is C The 149195726th base of human chromosome 5 is C The 149196638th base of human chromosome 5 is C The 149196916th base of human chromosome 5 is A The 149192166th base of human chromosome 5 is T The 149197747th base of human chromosome 5 is C The 149199467th base of human chromosome 5 is C The 149197609th base of human chromosome 5 is T The 149197815th base of human chromosome 5 is T The 149200932nd base of human chromosome 5 is G The 149190799th base of human chromosome 5 is G The 149190248th base of human chromosome 5 is C The 149203782nd base of human chromosome 5 is A The 149205992nd base of human chromosome 5 is G The 149201956th base of human chromosome 5 is C The 149208516th base of human chromosome 5 is G The 149206531st base of human chromosome 5 is G The base at position 149227540 on human chromosome 5 is T The 149204461st base of human chromosome 5 is C The 149192744th base of human chromosome 5 is G The 149189449th base of human chromosome 5 is G The 149205417th base of human chromosome 5 is C The 149196564th base of human chromosome 5 is C The 149200402nd base of human chromosome 5 is A The 149199656th base of human chromosome 5 is C The 149196513th base of human chromosome 5 is A The 149199889th base of human chromosome 5 is G The 149200920th base of human chromosome 5 is A The 149202168th base of human chromosome 5 is A The 149200043rd base of human chromosome 5 is T The 149203993rd base of human chromosome 5 is A The 149187322nd base of human chromosome 5 is G The 149204444th base of human chromosome 5 is C The 149178996th base of human chromosome 5 is T The 149179725th base of human chromosome 5 is T The 149185923 base of human chromosome 5 is C The 149187212th base of human chromosome 5 is C The base at position 149187640 on human chromosome 5 is G The 149183256th base of human chromosome 5 is G The 149234701st base of human chromosome 5 is G The 149236008th base of human chromosome 5 is G The 149164366th base of human chromosome 5 is G The base at position 149230730 of human chromosome 5 is C The 149186478th base of human chromosome 5 is A The 149162451st base of human chromosome 5 is G The 149162294th base of human chromosome 5 is G The 149212471st base of human chromosome 5 is G The 149179741st base of human chromosome 5 is C The 149159862nd base of human chromosome 5 is C The 149184905th base of human chromosome 5 is G The 149159107th base of human chromosome 5 is A The 149211392nd base of human chromosome 5 is C The 149182832nd base of human chromosome 5 is G The 149208768th base of human chromosome 5 is A The 16788327th base of human chromosome 9 is A The 16788333rd base of human chromosome 9 is T The 16788336th base of human chromosome 9 is A The 16788308th base of human chromosome 9 is C The 16788328th base of human chromosome 9 is G The 16815861st base of human chromosome 9 is A The 16825110th base of human chromosome 9 is C The 16789652nd base of human chromosome 9 is T The 16795159th base of human chromosome 9 is A The 16812810th base of human chromosome 9 is T The 16789024th base of human chromosome 9 is T The 16789436th base of human chromosome 9 is A The 16820923rd base of human chromosome 9 is C The 16795588th base of human chromosome 9 is A The 16795211th base of human chromosome 9 is G The 16,824,921st base of human chromosome 9 is C The 16788367th base of human chromosome 9 is C The 119564143rd base of human chromosome 10 is C The 119563401st base of human chromosome 10 is T The 119565538th base of human chromosome 10 is C The 119561969th base of human chromosome 10 is C The 119573178th base of human chromosome 10 is C The 119572403 base of human chromosome 10 is C The 119587425th base of human chromosome 10 is G The base at position 119584730 of human chromosome 10 is C The 119599727th base of human chromosome 10 is A The 119575974th base of human chromosome 10 is C The 119576317th base of human chromosome 10 is G The 119576318th base of human chromosome 10 is G The 119576319th base of human chromosome 10 is C The 119584861st base of human chromosome 10 is A The 119562387th base of human chromosome 10 is C The 119572476th base of human chromosome 10 is C The 119577677th base of human chromosome 10 is G The base at position 119601436 of human chromosome 10 is T The 119575798th base of human chromosome 10 is C The 119601939th base of human chromosome 10 is G The 119602316th base of human chromosome 10 is G The 119602424th base of human chromosome 10 is G The 119601743rd base of human chromosome 10 is G The 119586963rd base of human chromosome 10 is C The 119586186th base of human chromosome 10 is A The 119586231st base of human chromosome 10 is C The 119586178th base of human chromosome 10 is C The 119587158th base of human chromosome 10 is G The base at position 119591330 of human chromosome 10 is G The 119586980th base of human chromosome 10 is A The 119586462nd base of human chromosome 10 is C The 119592083rd base of human chromosome 10 is C The base at position 119595140 of human chromosome 10 is G The 119582802nd base of human chromosome 10 is C The 119591168th base of human chromosome 10 is C The 119581527th base of human chromosome 10 is G The 3548231st base of human chromosome 19 is A The 3542983rd base of human chromosome 19 is C The 3540539th base of human chromosome 19 is G

[0039] These bases are listed only as examples in Table 1, and although not specifically described, markers involved in pigmentation can also be derived from Tables 2 and 3 in the same way.

[0040] Furthermore, the markers of the present invention are markers that can determine the degree of increase or decrease in phenotype (pigmentation) in response to an increase in the minor allele of the base at the polymorphic site of the polymorphic marker in an individual. For example, among the markers shown in Table 1, when the base at position 149192846 on chromosome 5 of an individual is the minor allele G (rs17110447), the effect size is negative (-), and therefore pigmentation is determined to decrease. When the base at position 16795241 on chromosome 9 of an individual is the minor allele C (rs10810635), the effect size is positive (+), and therefore pigmentation is determined to increase, but the present invention is not limited to these.

[0041] Specifically, the single nucleotide polymorphism marker increases pigmentation when it contains at least one of the following bases, which are minor alleles, but is not limited to these. The 16795790th base of human chromosome 9 is C The 16795241st base of human chromosome 9 is C The 16794418th base of human chromosome 9 is A The 16806521st base of human chromosome 9 is C The base at position 16801450 on human chromosome 9 is T The 16808172nd base of human chromosome 9 is G The 16806694th base of human chromosome 9 is C The 16801743rd base of human chromosome 9 is A The base at position 16801120 of human chromosome 9 is C The 16788274th base of human chromosome 9 is G The 16788253rd base of human chromosome 9 is C The 16790074th base of human chromosome 9 is G The 16790968th base of human chromosome 9 is C The 16788363rd base of human chromosome 9 is G The 16790960th base of human chromosome 9 is G The 16799844th base of human chromosome 9 is T The 16793202nd base of human chromosome 9 is C The 16793104th base of human chromosome 9 is G The 16792350th base of human chromosome 9 is C The 16796252nd base of human chromosome 9 is G The 16792675th base of human chromosome 9 is C The 16791865th base of human chromosome 9 is T The 16787767th base of human chromosome 9 is C The 119568133rd base of human chromosome 10 is A The base at position 119570121 of human chromosome 10 is T The 119569921st base of human chromosome 10 is A The 119570915th base of human chromosome 10 is T The 119571832nd base of human chromosome 10 is A The 119572168th base of human chromosome 10 is A The 119547342nd base of human chromosome 10 is T The 119561946th base of human chromosome 10 is T The 119570716th base of human chromosome 10 is A The 119563422nd base of human chromosome 10 is A The 119544822nd base of human chromosome 10 is G The 119544385th base of human chromosome 10 is T The 119547279th base of human chromosome 10 is T The 119544027th base of human chromosome 10 is T The 119545571st base of human chromosome 10 is A The 119547081st base of human chromosome 10 is C The 119547669th base of human chromosome 10 is G The 119545287th base of human chromosome 10 is G The 119545401st base of human chromosome 10 is A The 119545101st base of human chromosome 10 is C The 119545375th base of human chromosome 10 is T The 119545741st base of human chromosome 10 is G The 119545762nd base of human chromosome 10 is C The 119546979th base of human chromosome 10 is C The 119545238th base of human chromosome 10 is C The 119546034th base of human chromosome 10 is T The 119546496th base of human chromosome 10 is T The 119546323 base of human chromosome 10 is G The 119552651st base of human chromosome 10 is A The 119566093rd base of human chromosome 10 is T The base at position 89985940 on human chromosome 16 is A The 89986760th base of human chromosome 16 is G The 89987201st base of human chromosome 16 is G The 89986608th base of human chromosome 16 is G The 89985177th base of human chromosome 16 is C The 89985441st base of human chromosome 16 is A The 89986025th base of human chromosome 16 is C The 89986154th base of human chromosome 16 is G The 89985222nd base of human chromosome 16 is G The 200473658th base of human chromosome 2 is T The 200475044th base of human chromosome 2 is G The 200492565th base of human chromosome 2 is G The 200492076th base of human chromosome 2 is C The 200484107th base of human chromosome 2 is G The 200478921st base of human chromosome 2 is G The 200491198th base of human chromosome 2 is C The 200491299th base of human chromosome 2 is A The base at position 200477380 of human chromosome 2 is T The 200477504th base of human chromosome 2 is T The 200477506th base of human chromosome 2 is C The 200484696th base of human chromosome 2 is G The 200485100th base of human chromosome 2 is C The 200487486th base of human chromosome 2 is A The 200491726th base of human chromosome 2 is C The 200491877th base of human chromosome 2 is G The 200484452nd base of human chromosome 2 is G The 200491187th base of human chromosome 2 is G The 200479539th base of human chromosome 2 is T The 200488306th base of human chromosome 2 is C The 200488785th base of human chromosome 2 is C The 200488905th base of human chromosome 2 is G The 200489109th base of human chromosome 2 is A The 200484657th base of human chromosome 2 is G The 200481019th base of human chromosome 2 is T The 200486976th base of human chromosome 2 is G The 200487539th base of human chromosome 2 is C The 200489964th base of human chromosome 2 is G The 200490260th base of human chromosome 2 is G The 200491038th base of human chromosome 2 is G The 200482025th base of human chromosome 2 is G The 200482231st base of human chromosome 2 is A The 200482513th base of human chromosome 2 is T The 200480777th base of human chromosome 2 is C The 200481498th base of human chromosome 2 is G The 200481506th base of human chromosome 2 is T The 200495743 base of human chromosome 2 is C The 200482881st base of human chromosome 2 is T The 200499444th base of human chromosome 2 is A The 200499255th base of human chromosome 2 is A The 200491272nd base of human chromosome 2 is G The 200474888th base of human chromosome 2 is A The 200478354th base of human chromosome 2 is C The 200484686th base of human chromosome 2 is T The 200485648th base of human chromosome 2 is C The 200498327th base of human chromosome 2 is T The 200501964th base of human chromosome 2 is G The 200499206th base of human chromosome 2 is G The 200500431st base of human chromosome 2 is T The 200500296th base of human chromosome 2 is C The 200506846th base of human chromosome 2 is T The 200492529th base of human chromosome 2 is C The 200501467th base of human chromosome 2 is A The 200505203 base of human chromosome 2 is G The 200494912th base of human chromosome 2 is G The 200496036th base of human chromosome 2 is C The 200497907th base of human chromosome 2 is G The 200499399th base of human chromosome 2 is G The 200501134th base of human chromosome 2 is C The 200499157th base of human chromosome 2 is G The 200498080th base of human chromosome 2 is G The 200490231st base of human chromosome 2 is A The 200497975th base of human chromosome 2 is A The 200501827th base of human chromosome 2 is C The 200489315th base of human chromosome 2 is A The 200497286th base of human chromosome 2 is T The 200494182nd base of human chromosome 2 is A The 200497711th base of human chromosome 2 is G The 200496814th base of human chromosome 2 is T The 200509555th base of human chromosome 2 is A The 200509556th base of human chromosome 2 is T The 200495510th base of human chromosome 2 is G The 200510641st base of human chromosome 2 is C The 200510941st base of human chromosome 2 is G

[0042] Furthermore, the single nucleotide polymorphism marker reduces pigmentation when it contains at least one of the following bases, which are minor alleles, but is not limited thereto. The 149192846th base of human chromosome 5 is G The 149191111th base of human chromosome 5 is T The 149195389th base of human chromosome 5 is C The 149196682nd base of human chromosome 5 is G The 149200603 base of human chromosome 5 is C The 149194923 base of human chromosome 5 is C The 149202206th base of human chromosome 5 is G The 149194485th base of human chromosome 5 is T The 149195603 base of human chromosome 5 is G The 149196090th base of human chromosome 5 is C The 149196234th base of human chromosome 5 is C The base at position 149205630 of human chromosome 5 is T The base at position 149210848 on human chromosome 5 is T The 149211868th base of human chromosome 5 is A The 149209546th base of human chromosome 5 is T The base at position 149212430 on human chromosome 5 is A The 149216304th base of human chromosome 5 is T The 149226633rd base of human chromosome 5 is A The 149216256th base of human chromosome 5 is T The 149228648th base of human chromosome 5 is T The 149213456th base of human chromosome 5 is G The 149204852nd base of human chromosome 5 is G The 149218886th base of human chromosome 5 is A The 149215213th base of human chromosome 5 is G The 149229822nd base of human chromosome 5 is T The 149231519th base of human chromosome 5 is T The 149233110th base of human chromosome 5 is A The 149233186th base of human chromosome 5 is T The 149216987th base of human chromosome 5 is G The 149199148th base of human chromosome 5 is A The base at position 149231830 of human chromosome 5 is G The 149195125th base of human chromosome 5 is G The 149232525th base of human chromosome 5 is G The base at position 149197230 of human chromosome 5 is C The 149232308th base of human chromosome 5 is A The 149196329th base of human chromosome 5 is A The 149230952nd base of human chromosome 5 is G The 149230745th base of human chromosome 5 is C The 149230787th base of human chromosome 5 is T The 149231786th base of human chromosome 5 is A The 149234235th base of human chromosome 5 is A The 149234236th base of human chromosome 5 is T The 149159174th base of human chromosome 5 is A The 149190810th base of human chromosome 5 is T The 149194785th base of human chromosome 5 is A The 149191547th base of human chromosome 5 is T The 149193133rd base of human chromosome 5 is T The 149195726th base of human chromosome 5 is T The 149196638th base of human chromosome 5 is T The 149196916th base of human chromosome 5 is G The 149192166th base of human chromosome 5 is C The 149197747th base of human chromosome 5 is G The 149199467th base of human chromosome 5 is T The 149197609th base of human chromosome 5 is C The 149197815th base of human chromosome 5 is C The 149200932nd base of human chromosome 5 is A The 149190799th base of human chromosome 5 is A The 149190248th base of human chromosome 5 is G The 149203782nd base of human chromosome 5 is G The 149205992nd base of human chromosome 5 is A The 149201956th base of human chromosome 5 is G The 149208516th base of human chromosome 5 is T The 149206531st base of human chromosome 5 is A The 149227540th base of human chromosome 5 is C The 149204461st base of human chromosome 5 is T The 149192744th base of human chromosome 5 is T The 149189449th base of human chromosome 5 is C The 149205417th base of human chromosome 5 is A The 149196564th base of human chromosome 5 is T The 149200402 base of human chromosome 5 is G The 149199656th base of human chromosome 5 is T The 149196513th base of human chromosome 5 is G The 149199889th base of human chromosome 5 is A The 149200920th base of human chromosome 5 is G The 149202168th base of human chromosome 5 is G The 149200043rd base of human chromosome 5 is C The 149203993rd base of human chromosome 5 is G The 149187322nd base of human chromosome 5 is A The 149204444th base of human chromosome 5 is T The 149178996th base of human chromosome 5 is C The 149179725th base of human chromosome 5 is C The 149185923rd base of human chromosome 5 is A The 149187212th base of human chromosome 5 is T The 149187640th base of human chromosome 5 is A The 149183256th base of human chromosome 5 is T The 149234701st base of human chromosome 5 is A The 149236008th base of human chromosome 5 is A The 149164366th base of human chromosome 5 is A The base at position 149230730 of human chromosome 5 is T The 149186478th base of human chromosome 5 is T The 149162451st base of human chromosome 5 is A The 149162294th base of human chromosome 5 is A The 149212471st base of human chromosome 5 is A The 149179741st base of human chromosome 5 is A The 149159862nd base of human chromosome 5 is G The 149184905th base of human chromosome 5 is T The 149159107th base of human chromosome 5 is G The 149211392nd base of human chromosome 5 is G The 149182832nd base of human chromosome 5 is C The 149208768th base of human chromosome 5 is G The 16788327th base of human chromosome 9 is G The 16788333rd base of human chromosome 9 is C The 16788336th base of human chromosome 9 is G The 16788308th base of human chromosome 9 is T The 16788328th base of human chromosome 9 is A The 16815861st base of human chromosome 9 is G The 16825110th base of human chromosome 9 is T The 16789652nd base of human chromosome 9 is C The 16795159th base of human chromosome 9 is G The 16812810th base of human chromosome 9 is C The 16789024th base of human chromosome 9 is C The 16789436th base of human chromosome 9 is G The 16820923rd base of human chromosome 9 is G The 16795588th base of human chromosome 9 is T The 16795211th base of human chromosome 9 is C The 16,824,921st base of human chromosome 9 is G The 16788367th base of human chromosome 9 is T The base at position 119564143 of human chromosome 10 is T The 119563401st base of human chromosome 10 is C The 119565538th base of human chromosome 10 is A The 119561969th base of human chromosome 10 is T The base at position 119573178 of human chromosome 10 is T The 119572403 base of human chromosome 10 is T The 119587425th base of human chromosome 10 is A The base at position 119584730 of human chromosome 10 is T The 119599727th base of human chromosome 10 is G The 119575974th base of human chromosome 10 is T The 119576317th base of human chromosome 10 is C The 119576318th base of human chromosome 10 is T The 119576319th base of human chromosome 10 is G The 119584861st base of human chromosome 10 is G The 119562387th base of human chromosome 10 is T The 119572476th base of human chromosome 10 is A The 119577677th base of human chromosome 10 is A The 119601436th base of human chromosome 10 is G The 119575798th base of human chromosome 10 is T The 119601939th base of human chromosome 10 is C The 119602316th base of human chromosome 10 is A The 119602424th base of human chromosome 10 is T The 119601743rd base of human chromosome 10 is A The 119586963rd base of human chromosome 10 is T The 119586186th base of human chromosome 10 is T The 119586231st base of human chromosome 10 is T The base at position 119586178 of human chromosome 10 is T The 119587158th base of human chromosome 10 is A The base at position 119591330 of human chromosome 10 is A The 119586980th base of human chromosome 10 is G The 119586462nd base of human chromosome 10 is A The 119592083rd base of human chromosome 10 is T The base at position 119595140 on human chromosome 10 is A The 119582802nd base of human chromosome 10 is T The 119591168th base of human chromosome 10 is A The 119581527th base of human chromosome 10 is A The 3548231st base of human chromosome 19 is G The 3542983rd base of human chromosome 19 is T The 3540539th base of human chromosome 19 is C

[0043] These bases are listed only as examples in Table 1, and although not specifically described, markers involved in pigmentation can also be derived from Tables 2 and 3 in the same way.

[0044] In the present invention, the "probe for detecting a diagnostic marker for the presence or absence of pigmentation of a skin type" means a composition that can be confirmed by a specific hybridization reaction with the polymorphic site of the above-mentioned gene to diagnose the presence or absence of skin pigmentation, and the specific method for the gene analysis may be any, and any gene detection method known in the technical field to which the present invention pertains may be used.

[0045] In the present invention, the "preparation for amplifying a marker for diagnosing the presence or absence of pigmentation in a skin type" refers to a composition that can diagnose the presence or absence of skin pigmentation by confirming the amplification of the polymorphic site of the above-mentioned gene, and specifically refers to a primer that specifically amplifies the polynucleotide of the marker for diagnosing the presence or absence of pigmentation in a skin type.

[0046] The primer used to amplify the polymorphic marker refers to a single-stranded oligonucleotide that acts as an initiation point for template-directed DNA synthesis under appropriate conditions (e.g., four different nucleoside triphosphates and a polymerization agent such as DNA or RNA polymerase or reverse transcriptase) in an appropriate buffer at an appropriate temperature. The appropriate length of the primer varies depending on the intended use, but is usually 15 to 30 nucleotides. Shorter primer molecules generally require lower temperatures to form stable hybrids with the template. The primer sequence does not need to be completely complementary to the template, but must be sufficiently complementary to be able to hybridize with the template.

[0047] In the present invention, a "primer" refers to a short base sequence with a free 3' hydroxyl group that can form a base pair with a complementary template and serve as a starting point for copying the template. A primer can initiate DNA synthesis in the presence of a polymerization reagent (i.e., DNA polymerase or reverse transcriptase) and four different nucleoside triphosphates in an appropriate buffer and temperature. PCR amplification can be performed, and skin type can be predicted based on whether or not the desired product is produced. PCR conditions and the lengths of sense and antisense primers may be varied based on those known in the art.

[0048] The probes or primers of the present invention can be chemically synthesized using the phosphoramidite solid support method or other known methods. Additionally, such nucleic acid sequences can be modified using a number of means known in the art. Examples of such modifications include, but are not limited to, methylation, "capping," substitution of at least one natural nucleotide with its analog, and internucleotide modifications, such as uncharged linkers (e.g., methylphosphonates, phosphotriesters, phosphoramidates, carbamates, etc.) or charged linkers (e.g., phosphorothioates, phosphorodithioates, etc.).

[0049] In yet another aspect, the present invention provides a kit for diagnosing the presence or absence of skin pigmentation, which comprises the composition for diagnosing the presence or absence of skin pigmentation. The kit may be, but is not limited to, an RT-PCR kit or a DNA chip kit.

[0050] The kit of the present invention can diagnose skin type by amplifying SNP polymorphism markers, which are markers for diagnosing skin type, or by determining the expression level of SNP polymorphism markers based on mRNA expression levels. As a specific example, the kit for measuring the mRNA expression level of a skin-type diagnostic marker in the present invention may be a kit containing essential elements necessary for performing RT-PCR. The RT-PCR kit may contain, in addition to each primer pair specific to the gene of the skin-type diagnostic marker, a test tube or other suitable container, a reaction buffer (with various pH and magnesium concentrations), deoxynucleotides (dNTPs), enzymes such as Taq polymerase and reverse transcriptase, DNase, RNAse inhibitor, DEPC water (DEPC-water), sterile water, etc. It may also contain a primer pair specific to a gene used as a quantitative control. More specifically, the kit of the present invention may be a skin-type diagnostic kit containing essential elements necessary for using a DNA chip. A DNA chip kit is generally a flat solid support plate, typically glass no larger than a microscope slide, on which nucleic acid species are attached in a gridded array. The nucleic acids are arranged in a uniform pattern on the surface of the chip, and the kit is a tool that enables massively parallel analysis by causing multiple hybridization reactions between the nucleic acids on the DNA chip and complementary nucleic acids contained in a solution applied to the surface of the chip.

[0051] Yet another aspect of the present invention provides a microarray for diagnosing the presence or absence of pigmentation in skin types, comprising the composition for diagnosing the presence or absence of skin pigmentation.

[0052] The microarray may contain DNA or RNA polynucleotides. The microarray consists of a conventional microarray, except that the probe polynucleotide contains the polynucleotide of the present invention.

[0053] Methods for fabricating microarrays by immobilizing probe polynucleotides on a substrate are well known in the art. The term "probe polynucleotide" refers to a hybridizing polynucleotide, i.e., an oligonucleotide that binds in a sequence-specific manner to complementary strands of nucleic acid. The probes of the present invention are allele-specific probes, which hybridize to DNA fragments from one component but not to fragments from the other component, where a polymorphic site exists in nucleic acid fragments derived from two members of the same species. In this case, the hybridization conditions must be sufficiently stringent to exhibit significant differences in hybridization intensity between alleles and hybridize only to one of the alleles. This induces favorable hybridization differences between different allele forms. The probes of the present invention can be used in methods for diagnosing skin types by detecting alleles. Diagnostic methods include detection methods based on nucleic acid hybridization, such as Southern blotting. In methods using DNA chips, the probes may be provided in a form pre-bound to the DNA chip substrate. The hybridization is typically performed under stringent conditions, such as a salt concentration of 1 M or less and a temperature of 25°C or higher. For example, conditions of 5xSSPE (750 mM NaCl, 50 mM Na Phosphate, 5 mM EDTA, pH 7.4) at 25 to 30°C are suitable for hybridization of allele-specific probes.

[0054] The process of immobilizing probe polynucleotides for skin diagnosis of the present invention on a substrate can also be easily carried out using such conventional techniques. Furthermore, nucleic acid hybridization on a microarray and detection of hybridization results are well known in the art. Regarding the detection, for example, a nucleic acid sample can be labeled with a labeling substance that generates a detectable signal, including a fluorescent substance such as Cy3 or Cy5, and then hybridized to a microarray to detect the signal generated from the labeling substance, thereby detecting the hybridization results.

[0055] Yet another aspect of the present invention provides a method for providing information regarding the presence or absence of skin pigmentation, comprising: (a) a step of amplifying or hybridizing with a probe a polymorphic site of the single nucleotide polymorphism marker in DNA obtained from a sample isolated from an individual; and (b) a step of confirming the base of the polymorphic site amplified or hybridized in step (a).

[0056] In the present invention, the term "individual" refers to a subject to be diagnosed for the presence or absence of skin pigmentation. DNA can be obtained from samples such as, but not limited to, hair, urine, blood, various body fluids, isolated tissues, isolated cells, and saliva.

[0057] The method for obtaining genomic DNA in step (a) may be any method known to those skilled in the art.

[0058] The step of amplifying the polymorphic site of the single nucleotide polymorphism marker from the DNA obtained in step (a) or hybridizing it with a probe may be performed using any method known to those skilled in the art. For example, the target nucleic acid may be amplified by PCR and purified. Other methods that may be used include ligase chain reaction (LCR) (Non-Patent Documents 6 and 7), transcription amplification (Non-Patent Document 8), self-sustained sequence replication (Non-Patent Document 9), and nucleic acid sequence-based amplification (NASBA).

[0059] In the above-mentioned method, the determination of the base at the polymorphic site in step (b) includes, but is not limited to, sequencing analysis, microarray hybridization, allele-specific PCR, dynamic allele-specific hybridization (DASH), PCR extension analysis, SSCP, PCR-RFLP analysis or TaqMan method, SNPlex platform (Applied Biosystems), mass spectrometry (e.g., Sequenom's MassARRAY system), mini-sequencing, Bio-Plex system (BioRad), CEQ and SNPstream system (Beckman), Molecular Inversion Probe array technology (e.g., Affymetrix GeneChip), and BeadArray Technologies (e.g., Illumina GoldenGate and Infinium assays). By using the above method or other methods available to those skilled in the art, at least one allele at a polymorphic marker, including a microsatellite, SNP, or other type of polymorphic marker, is identified. The base at such a polymorphic site can be determined, specifically, by using an SNP chip.

[0060] The above method further includes, but is not limited to, (c) determining that pigmentation is increased or decreased when the base of the amplified or hybridized polymorphic site includes at least one base of a minor allele in the single nucleotide polymorphism marker, and also includes, but is not limited to, (c) determining that pigmentation is increased or decreased when the base of the amplified or hybridized polymorphic site includes at least one base of a major allele in the single nucleotide polymorphism marker.

[0061] In the present invention, the term "SNP chip" refers to a type of DNA microarray that can simultaneously identify hundreds of thousands of SNP bases.

[0062] The TaqMan method includes the steps of: (1) designing and preparing primers and TaqMan probes so as to amplify the desired DNA fragment; (2) labeling probes for different alleles with FAM dye and VIC dye (Applied Biosystems); (3) using the DNA as a template and performing PCR using the primers and probes; (4) analyzing and confirming the TaqMan analysis plate after the PCR reaction is completed using a nucleic acid analyzer; and (5) determining the genotype of the polynucleotide in step (1) from the analysis results.

[0063] The sequencing analysis can be performed using a conventional method for determining base sequences and can be carried out using an automated genetic analyzer. Allele-specific PCR refers to a PCR method in which the base at the SNP location is designated as the 3'-terminus and a primer set containing a designed primer is used to amplify a DNA fragment at the SNP location. The principle of this method is that, for example, when a specific base is substituted from A to G, a primer containing the A as the 3'-terminus base and a reverse primer amplifying a DNA fragment of an appropriate size are designed and a PCR reaction is performed. If the base at the SNP location is A, the amplification reaction proceeds normally and a band at the desired position is observed. However, if the base is substituted with G, the primer complementarily binds to the template DNA, but the 3'-terminus does not complementarily bind, resulting in an incomplete amplification reaction. DASH can be performed using conventional methods, specifically, methods such as PRINCE.

[0064] On the other hand, PCR extension analysis can be performed by first amplifying a DNA fragment containing the base where the single nucleotide polymorphism is located with a primer pair, then inactivating all nucleotides added to the reaction by dephosphorylation, and then adding an SNP-specific extension primer, a dNTP mixture, dideoxynucleotides, a reaction buffer, and DNA polymerase to perform a primer extension reaction. Here, the base adjacent to the 5' side of the base where the SNP is located is considered to be the 3' end of the extension primer, and the dNTP mixture excludes nucleic acids having the same base as the dideoxynucleotide, and the dideoxynucleotide is selected from one of the bases that indicate an SNP. For example, if an A to G substitution occurs, adding a mixture of dGTP, dCTP, and TTP and ddATP to the reaction will allow the primer to be extended by the DNA polymerase at the base where the substitution occurred, and the primer extension reaction will be terminated by ddATP at the position where the A base first appears after several bases. If the substitution does not occur, the extension reaction terminates at that position, and the type of base indicating the SNP can be determined by comparing the lengths of the extended primers as described above.

[0065] Here, as for the detection method, when the extension primer or dideoxynucleotide is fluorescently labeled, the SNP can be detected by detecting fluorescence using a genetic analyzer used for general base sequence determination (e.g., Model 3700 manufactured by ABI), and when the extension primer or dideoxynucleotide is unlabeled, the SNP can be detected by measuring the molecular weight using the MALDI-TOF (matrix assisted laser desorption ionization-time of flight) method. [Example]

[0066] The present invention will be described in more detail below with reference to examples. However, these examples are merely illustrative of the present invention and are not intended to limit the scope of the present invention.

[0067] We attempted to identify genomic sites (gene mutations) that cause differences in the degree (value) of facial skin pigmentation in Korean women according to their genetic information. The present invention aims to identify genomic sites (gene mutations) related to pigmentation, and utilizes a microarray genotyping chip (manufactured by Illumina), which allows screening at the whole genome level without pre-selecting candidate genes.

[0068] In the present invention, an image-based skin diagnostic device (Janus3 by PIE) was used to evaluate the degree of pigmentation, and the data was corrected for age and the principal component values ​​of the population in order to minimize external effects that affect the degree (value) of skin pigmentation.

[0069] To confirm the association between genomic sites (gene mutations) and the degree of skin pigmentation (values), linear regression analysis was used to quantify the correlation significance and genetic effect. [Example]

[0070] Skin characterization and gene sampling To derive genetic polymorphism markers that can explain the degree of general skin pigmentation, healthy Korean women in their 20s to 70s were recruited. Furthermore, all subjects undergoing skin measurement washed their faces with cleanser or soap and waited 30 minutes without applying any products to allow their skin to adapt to the measurement environment. The degree of skin pigmentation was then assessed using an image-based skin diagnostic device (PIE Janus3) (measurements and analysis were performed according to the device manufacturer's instructions).

[0071] The degree of skin pigmentation in a typical individual (having the major allele / major allele) refers to the average facial degree of skin pigmentation measured in 17,019 subjects in whom two alleles are observed at the same locus (base), and the value was derived from the proportion of areas within the analyzed area that were observed to be relatively black or brown compared to the surrounding skin color.

[0072] Gene collection was performed by collecting saliva, and for effective gene collection, all subjects were instructed not to consume any food or drink, including water, for 30 minutes prior to collection.

[0073] Subjects were excluded if they were: (1) pregnant, breastfeeding, or planning to become pregnant within the next six months; (2) had used topical skin preparations containing steroids for the treatment of skin diseases for more than one month; (3) had participated in the same study less than six months ago; (4) had sensitive or hypersensitive skin; (5) had abnormal skin findings such as moles, acne, erythema, or telangiectasia in the test area; (6) had used the same or similar cosmetics or medicines in the test area within three months of the start of the study; (7) had undergone treatment (dermabrasion, Botox, or other skin management) in the test area or were planning to do so within the last six months; (8) had a chronic wasting disease (asthma, diabetes, hypertension, etc.); (9) had atopic dermatitis; or (10) were otherwise deemed by the principal investigator to be difficult to participate in the study. [Example]

[0074] Genotyping by skin characteristics Human genomic DNA was extracted from saliva for genetic analysis using the QIAmp mini prep kit (QIAGEN). The quality of the DNA was confirmed by band testing on a 1% agarose gel in 1x TAE at an absorbance (OD260 / 280) of 1.7 and a concentration of 50 ng / ul. Gene analysis was performed only on samples that passed the quality check.

[0075] Genetic analysis was performed using Illumina's microarray genotyping chip. Specifically, the genes of the subjects were analyzed using the company's global screening array product.

[0076] Genetic analysis experiments using Illumina's microarray genotyping chip were performed according to the provided instructions, and the genomic DNA amplification, DNA fragmentation, precipitation, hybridization, staining, washing, coating, and scanning processes were performed using the provided reagents.

[0077] After the experiment, the microarray genotyping chips were scanned using iScan Control Software (Illumina). After scanning, an idat file was automatically generated, and data quality control (sample call rate 98%, marker call rate 98%) and genetic information confirmation were performed using the GenomeStudio (Illumina) program.

[0078] In this experiment, only data that had undergone data quality control after genetic analysis was used. [Example]

[0079] Derivation of genetic polymorphism markers significantly associated with the degree of skin pigmentation through genotyping by skin type To identify genetic polymorphisms significantly associated with skin pigmentation, linear regression analysis was performed using the genetic polymorphisms analyzed using PLINK v 1.90 and the SNP & Variation suite (Golden Helix, Inc., Bozeman, Montana, USA) programs.

[0080] To obtain further information on genetic polymorphisms, we performed imputation analysis using the Beagle v5.1 program, utilizing the genetic polymorphism markers confirmed by the experiment. The reference data for this analysis was information registered in the 1000 Genomes Project, an international open genome database.

[0081] Imputation is a statistical technique for inferring unanalyzed gene polymorphism marker information based on gene polymorphism marker information obtained through experiments.

[0082] To quality control the analyzed genetic polymorphism markers, we limited each genetic polymorphism marker to those exceeding the minor allele frequency or 0.01 and Hardy-Weinberg equilibrium level or 0.000001.

[0083] The significance of genetic polymorphism markers showing association with the degree of skin pigmentation was evaluated by linear regression analysis F-statistics, with the criterion set at P-value<0.0001.

[0084] In order to minimize external effects that affect the degree of skin pigmentation and to obtain the effect of genetic information, the degree of skin pigmentation is adjusted for age or BMI information, or information on lifestyle habits (drinking, smoking, eating habits, sleeping habits, etc.) and used in the analysis (for example, by performing linear regression analysis).

[0085] A large number of genetic polymorphism markers were identified that were significantly associated with the degree of skin pigmentation, and these genetic polymorphism markers were confirmed to be located primarily on chromosomes 2, 5, 9, 10, 16, and 19 in the human genome.

[0086] A list of SNP markers significantly associated with skin pigmentation is shown in Tables 1 to 3.

[0087] Table 1-1 Table 1-2 Table 1-3 Table 1-4 Table 1-5 Table 1-6 Table 1-7 Table 1-8 Table 1-9 Table 1-10 Table 1-11 Table 1-12 Table 1-13 Table 1-14 Table 1-15 Table 1-16 Table 1-17 Table 1-18 Table 1-19 Table 1-20 Table 1-21 Table 1-22 Table 1-23 Table 1-24 Table 1-25 Table 1-26 Table 1-27 Table 1-28 Table 1-29 Table 1-30

[0088] Table 2-1 Table 2-2 Table 2-3 Table 2-4 Table 2-5 Table 2-6 Table 2-7 Table 2-8 Table 2-9 Table 2-10 Table 2-11 Table 2-12 Table 2-13 Table 2-14 Table 2-15 Table 2-16 Table 2-17 Table 2-18 Table 2-19 Table 2-20 Table 2-21 Table 2-22 Table 2-23 Table 2-24 Table 2-25 Table 2-26 Table 2-27 Table 2-28 Table 2-29 Table 2-30 Table 2-31 Table 2-32 Table 2-33 Table 2-34 Table 2-35 Table 2-36 Table 2-37 Table 2-38 Table 2-39 Table 2-40 Table 2-41 Table 2-42 Table 2-43 Table 2-44 Table 2-45 Table 2-46 Table 2-47 Table 2-48 Table 2-49 Table 2-50 Table 2-51 Table 2-52 Table 2-53 Table 2-54 Table 2-55 Table 2-56 Table 2-57 Table 2-58 Table 2-59 Table 2-60 Table 2-61 Table 2-62 Table 2-63 Table 2-64 Table 2-65 Table 2-66 Table 2-67 Table 2-68 Table 2-69 Table 2-70 Table 2-71 Table 2-72 Table 2-73 Table 2-74 Table 2-75

[0089] Table 3-1 Table 3-2 Table 3-3 Table 3-4 Table 3-5 Table 3-6 Table 3-7 Table 3-8 Table 3-9 Table 3-10 Table 3-11 Table 3-12 Table 3-13 Table 3-14 Table 3-15 Table 3-16 Table 3-17 Table 3-18 Table 3-19 Table 3-20 Table 3-21 Table 3-22 Table 3-23 Table 3-24 Table 3-25 Table 3-26 Table 3-27 Table 3-28 Table 3-29 Table 3-30 Table 3-31 Table 3-32 Table 3-33 Table 3-34 Table 3-35 Table 3-36 Table 3-37 Table 3-38 Table 3-39 Table 3-40 Table 3-41 Table 3-42 Table 3-43 Table 3-44 Table 3-45 Table 3-46 Table 3-47 Table 3-48 Table 3-49 Table 3-50 Table 3-51 Table 3-52 Table 3-53 Table 3-54 Table 3-55 Table 3-56 Table 3-57 Table 3-58 Table 3-59 Table 3-60 Table 3-61 Table 3-62 Table 3-63 Table 3-64 Table 3-65 Table 3-66 Table 3-67 Table 3-68 Table 3-69 Table 3-70 Table 3-71 Table 3-72 Table 3-73 Table 3-74 Table 3-75 Table 3-76 Table 3-77 Table 3-78 Table 3-79 Table 3-80 Table 3-81 Table 3-82 Table 3-83 Table 3-84 Table 3-85 Table 3-86 Table 3-87 Table 3-88 Table 3-89 Table 3-90 Table 3-91 Table 3-92 Table 3-93 Table 3-94 Table 3-95 Table 3-96 Table 3-97 Table 3-98 Table 3-99 Table 3-100 Table 3-101 Table 3-102 Table 3-103 Table 3-104 Table 3-105 Table 3-106 Table 3-107 Table 3-108 Table 3-109 Table 3-110 Table 3-111 Table 3-112 Table 3-113 Table 3-114 Table 3-115 Table 3-116 Table 3-117 Table 3-118 Table 3-119 Table 3-120 Table 3-121 Table 3-122 Table 3-123 Table 3-124 Table 3-125 Table 3-126 Table 3-127 Table 3-128 Table 3-129 Table 3-130 Table 3-131 Table 3-132 Table 3-133 Table 3-134 Table 3-135 Table 3-136 Table 3-137 Table 3-138 Table 3-139 Table 3-140 Table 3-141 Table 3-142 Table 3-143 Table 3-144 Table 3-145 Table 3-146 Table 3-147 Table 3-148 [Table 3-149] [Table 3-150] [Table 3-151] [Table 3-152] [Table 3-153] [Table 3-154] [Table 3-155] [Table 3-156] [Table 3-157] [Table 3-158]

[0090] As a result, genetic mutations primarily associated with skin pigmentation were identified at seven genomic sites.

[0091] Among the many gene variants, the gene variants showing the highest association significance representing each genomic site are as follows: [BNC2 at 9p22 (rs16935073; P-value = 4.02Х10 -35 ), PPARGC1B at 5q32 (rs26127; P-value = 6.40Х10 -59 ), 10q26 (rs11198143; P-value = 9.24Х10 -41), FANCA at 16q24 (rs12921383; P-value = 1.07Х10 -43 ), 2q33 (rs4675687; P-value = 2.90Х10 -22 ), and MFSD12 at 19p13 (rs2240751; P-value = 2.12Х10 -10 ), 11q22 (rs4794701; P-value = 7.29Х10 -21 )]

[0092] From the above description, those skilled in the art to which the present invention pertains will understand that the present invention can be embodied in other specific forms without changing the technical spirit or essential features thereof. It should be understood that the above examples are merely illustrative and not limiting. The present invention should be construed as including all modifications and variations derived from the meaning and scope of the claims, rather than the specification, and their equivalents.

Claims

1. A composition for diagnosing the presence or absence of skin pigmentation, comprising a probe for detecting or an agent for amplifying at least one single nucleotide polymorphism (SNP) marker for diagnosing the presence or absence of skin pigmentation selected from Tables 1 to 3.

2. The composition according to claim 1, wherein the single nucleotide polymorphism marker for diagnosing the presence or absence of skin pigmentation further comprises at least one polynucleotide selected from the group consisting of polynucleotides corresponding to at least one single nucleotide polymorphism marker selected from any of Tables 1 to 3 and complementary polynucleotides thereof.

3. A kit for diagnosing the presence or absence of skin pigmentation, comprising the composition according to claim 1 or 2.

4. 4. The kit for diagnosing the presence or absence of skin pigmentation according to claim 3, wherein the kit is an RT-PCR kit or a DNA chip kit.

5. A microarray for diagnosing the presence or absence of skin pigmentation, comprising the single nucleotide polymorphism (SNP) marker for diagnosing the presence or absence of skin pigmentation according to claim 1.

6. (a) amplifying or hybridizing with a probe a polymorphic site of the single nucleotide polymorphism marker for diagnosing the presence or absence of skin pigmentation according to claim 1 in DNA obtained from a sample isolated from an individual; (b) confirming the base of the polymorphic site amplified or hybridized in step (a).

7. The method for providing information relating to the presence or absence of skin pigmentation according to claim 6 , wherein the sample is hair, urine, blood, various body fluids, isolated tissue, isolated cells, or saliva.

8. 7. The method for providing information relating to the presence or absence of skin pigmentation according to claim 6, wherein the amplification and confirmation of the polymorphic site are carried out using an SNP chip.

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