A SNP molecular marker combination for evaluating genetic risk of vkh disease and application thereof

Abstract

This invention belongs to the field of biodetection technology, specifically relating to a combination of SNP molecular markers for assessing the genetic risk of VKH disease and its application. This SNP molecular marker combination consists of 22 SNP molecular markers. Based on this SNP molecular marker combination, the AUC value for assessing the genetic risk of VKH disease can reach 0.85, indicating high accuracy. It can assess genetic susceptibility before the onset of clinical symptoms, making it suitable for early screening and risk stratification; it reduces reliance on physician subjective experience and improves the objectivity and stability of VKH disease risk assessment.

Description

Technical Field

[0001] This invention belongs to the field of biological detection technology, specifically relating to a combination of SNP molecular markers for assessing the genetic risk of VKH disease and its application. Background Technology

[0002] Vogt-Koyanagi-Harada (VKH) disease is an autoimmune disease characterized by bilateral uveitis, often accompanied by involvement of the auditory, cutaneous, and central nervous systems. It is characterized by insidious onset, rapid progression, and a high risk of blindness. Currently, clinical diagnosis of VKH relies primarily on a comprehensive assessment of typical fundus findings, imaging examinations, and multi-system clinical symptoms. However, these diagnostic methods are highly dependent on the professional experience and judgment of clinicians, and are difficult to identify in the early stages of the disease or in patients with atypical clinical presentations, easily leading to missed or misdiagnosis, hindering early intervention and accurate risk stratification.

[0003] Existing research indicates that VKH disease has a significant genetic susceptibility, particularly closely related to loci in the human leukocyte antigen (HLA) region. However, traditional genetic studies often focus on single or a few genetic loci, making it difficult to systematically reflect the polygenic inheritance characteristics and complex genetic structure of VKH disease. Furthermore, current genetic research findings have not yet developed stable, quantifiable methods for assessing individual genetic risk, and there is a lack of systematic technical means to integrate the effects of multiple susceptibility loci, limiting the practical application of genetic information in clinical risk prediction and early screening.

[0004] Therefore, current technologies still lack a method for systematically screening genetic susceptibility loci for VKH at the whole-genome level and effectively integrating the effects of multiple genetic variation loci to achieve individual-level genetic risk assessment. In other words, existing technologies generally suffer from limited predictive ability, high subjectivity in assessment results, lack of standardization, and insufficient clinical translation. There is an urgent need for a highly accurate, objective, stable, and applicable VKH genetic risk assessment scheme suitable for early screening and risk stratification. Summary of the Invention

[0005] Based on this, the present invention aims to provide a combination of SNP molecular markers for assessing the genetic risk of VKH disease and its application. The combination of SNP molecular markers consists of 22 SNP molecular markers and is used to assess the genetic risk of VKH disease. The AUC value can reach 0.85, which is highly accurate.

[0006] To achieve the above objectives, the present invention can adopt the following technical solutions: In one aspect, this invention provides a combination of SNP molecular markers for assessing the genetic risk of VKH disease. Information on the combination of SNP molecular markers is shown in Table 1 below.

[0007] In another aspect, the present invention provides a reagent or kit for assessing the genetic risk of VKH disease, the reagent or kit comprising reagents for detecting the above-mentioned combination of SNP molecular markers.

[0008] Preferably, in the above reagents or kits, the reagents used to detect SNP molecular marker combinations include: primer pairs that specifically amplify SNP sites; and / or probes that specifically bind to SNP sites.

[0009] Preferably, the above reagents or kits further contain one or more of the following components: PCR reaction solution, DNA polymerase, dNTPs, positive control or negative control.

[0010] In another aspect, the present invention provides the application of the above-mentioned SNP molecular marker combination reagent in the preparation of reagents or kits for assessing the genetic risk of VKH disease.

[0011] In another aspect, the present invention provides a VKH disease genetic risk assessment system, comprising: The data acquisition module is used to acquire the genotype data of each SNP locus in the above-mentioned SNP molecular marker combination of the target individual; The storage module stores the pre-determined effect weights for each SNP locus. βi ; The calculation module is used to calculate the polygenic risk score (PRS) according to the following formula: ,in, Gi The encoded value determined based on the genotype data; An assessment module is used to assess the genetic risk of VKH disease in the target individual based on the polygenic risk score.

[0012] Preferably, in the above-mentioned VKH disease genetic risk assessment system, the effect weight of each SNP locus is... βi The results are shown in Table 1 below.

[0013] Preferably, in the above-mentioned VKH disease genetic risk assessment system, the coded value in the calculation module... Gi According to the additive inheritance model, when the target individual is homozygous for the effect allele at the stated SNP locus... Gi =2; when the target individual is heterozygous. Gi =1; when the target individual is homozygous for the reference allele. Gi =0.

[0014] Preferably, in the above-mentioned VKH disease genetic risk assessment system, the assessment module is configured to: compare the calculated PRS value with a preset threshold; if the PRS value is higher than the threshold, output the result that the target individual has a high genetic risk of VKH disease; if the PRS value is lower than the threshold, output the result that the target individual has a low genetic risk of VKH disease.

[0015] Preferably, in the above-mentioned VKH disease genetic risk assessment system, the threshold is 1.14.

[0016] In another aspect, the present invention provides a computer-readable storage medium having a computer program stored thereon, wherein the computer program, when executed by a processor, performs the following steps: (a) Obtain the genotype data of each SNP locus in the above-mentioned SNP molecular marker combination for the target individual; (b) Calculate the polygenic risk score (PRS) according to the following formula: ,in, βi is The pre-determined effect weight of the i-th SNP site Gi The encoded value determined based on the genotype data; (c) Assess the genetic risk of VKH disease in target individuals based on polygenic risk scores.

[0017] The beneficial effects of this invention include at least the following: the SNP molecular marker combination provided by this invention can be used to assess the genetic risk of VKH disease, with an AUC value of up to 0.85, indicating high accuracy. It can assess genetic susceptibility before the onset of clinical symptoms of the disease, and is suitable for early screening and risk stratification; it reduces reliance on doctors' subjective experience and improves the objectivity and stability of VKH disease risk assessment. Attached Figure Description

[0018] Figure 1 This is a schematic diagram of the ROC curve of the VKH disease risk prediction model based on PRS scores on an external validation dataset. Detailed Implementation

[0019] The embodiments described are provided to better illustrate the present invention, but are not intended to limit the scope of the invention to the embodiments described. Therefore, non-essential improvements and adjustments made to the embodiments by those skilled in the art based on the above description are still within the scope of protection of the present invention.

[0020] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit this disclosure. Singular expressions include plural expressions unless they have a distinct meaning in the context. As used herein, it should be understood that terms such as “comprising,” “having,” “including,” are intended to indicate the presence of features, numbers, operations, components, parts, elements, materials, or combinations thereof. The terminology of the invention is disclosed in the specification and is not intended to exclude the possibility that one or more other features, numbers, operations, components, parts, elements, materials, or combinations thereof may be present or added. As used herein, “ / ” may be interpreted as “and” or “or,” depending on the context.

[0021] In a first aspect, embodiments of the present invention provide a combination of SNP molecular markers for assessing the genetic risk of VKH disease, and the information of the SNP molecular marker combination is shown in Table 1 below.

[0022] It should be noted that the SNP molecular marker combination in this invention was obtained through large-sample VKH disease case-control association analysis and is used to assess an individual's genetic risk of developing VKH disease. This SNP molecular marker combination contains 22 SNP loci, widely distributed across 14 chromosomes (1, 2, 4, 5, 6, 7, 9, 10, 11, 12, 13, 16, 19, and 22). Chromosome 6 contains 4 loci, which are presumed to be closely associated with immune regulatory pathway genes related to VKH disease. The remaining loci correspond to different genetic regulatory regions. The synergistic effect of these SNP loci comprehensively covers the genetic susceptibility sites for VKH disease, avoiding the limitations of single SNP locus assessment. A1 / A2 represent the two alleles of each SNP locus, providing clear target information for subsequent genotyping and risk score calculation. This combination has the advantages of high specificity, high accuracy, and broad coverage, and can be used for early genetic risk screening, high-risk population stratification, and disease risk prediction for VKH disease.

[0023] Secondly, embodiments of the present invention provide a reagent or kit for assessing the genetic risk of VKH disease, the reagent or kit containing reagents for detecting the above-mentioned SNP molecular marker combinations.

[0024] It should be noted that the reagents or kits in this invention use the above-mentioned combination of SNP molecular markers as detection targets, which can quickly and accurately detect the genotypes of 22 SNP loci in the target individual, providing reliable detection data support for the genetic risk assessment of VKH disease.

[0025] In some specific examples, the reagents or kits described above used to detect SNP molecular marker combinations include: primer pairs that specifically amplify SNP sites; and / or probes that specifically bind to SNP sites.

[0026] It should be noted that the primer pairs specifically amplifying SNP sites are designed for each of the 22 SNP sites. Each primer pair specifically binds to the upstream and downstream conserved sequences of the corresponding SNP site, enabling precise amplification of fragments containing the target SNP site and avoiding detection errors caused by non-specific amplification. These primer pairs are compatible with PCR, sequencing, and other detection methods. The probes specifically binding to SNP sites can be designed for different alleles (A1 / A2) at each SNP site (e.g., fluorescent probes, nucleic acid probes), enabling rapid and specific identification of the target allele and rapid genotyping. These probes are compatible with efficient detection platforms such as qPCR and gene chips. Both reagents can be used alone or in combination, allowing for flexible selection based on detection needs and equipment, ensuring the accuracy and reliability of test results while simplifying the detection process and improving efficiency.

[0027] In some specific examples, the kits described above also contain one or more of the following components: PCR reaction solution, DNA polymerase, dNTPs, positive control or negative control.

[0028] It should be noted that adding the above components further improves the practicality of the kit. Specifically, the PCR reaction solution provides a stable buffer environment for the amplification reaction, adjusting the pH and ion concentration of the reaction system to ensure smooth primer binding and DNA amplification; DNA polymerase is the core enzyme of the amplification reaction, catalyzing the extension of the DNA chain to ensure efficient amplification of the target fragment; dNTPs (deoxynucleoside triphosphates) serve as raw materials for DNA synthesis, providing the necessary nucleotides for the amplification reaction; positive controls (standard DNA samples containing known SNP genotypes) are used to verify the effectiveness of the detection system and ensure the normal operation of the detection process; negative controls (DNA samples without the target SNP site) are used to eliminate false positive results caused by experimental contamination. The synergistic effect of each component further improves the accuracy, reliability, and repeatability of the detection results, reduces experimental errors, and makes the kit suitable for routine clinical testing and research applications.

[0029] Thirdly, embodiments of the present invention provide the application of the above-mentioned SNP molecular marker combination reagent in the preparation of reagents or kits for assessing the genetic risk of VKH disease.

[0030] It should be noted that combining the 22 SNP molecular markers in this invention with VKH disease genetic risk assessment provides a novel technical approach for VKH disease genetic risk screening. Its applications are wide-ranging, including clinical screening of high-risk groups for VKH disease (such as individuals with a family history of VKH), disease risk prediction, genetic counseling, and research into the genetic mechanisms of VKH disease, providing a scientific basis for early intervention and individualized prevention and treatment.

[0031] Fourthly, embodiments of the present invention provide a VKH disease genetic risk assessment system, comprising: The data acquisition module is used to acquire the genotype data of each SNP locus in the above-mentioned SNP molecular marker combination of the target individual; The storage module stores the pre-determined effect weights for each SNP locus. βi ; The calculation module is used to calculate the polygenic risk score (PRS) according to the following formula: ,in, Gi The encoded value determined based on the genotype data; An assessment module is used to assess the genetic risk of VKH disease in the target individual based on the polygenic risk score.

[0032] It should be noted that in the VKH disease genetic risk assessment system of this invention, the data acquisition module can be connected to various testing platforms (such as sequencers and gene chip detectors) to quickly obtain genotype data of 22 SNP loci for the target individual, ensuring the convenience and accuracy of data acquisition; the storage module pre-stores the effect weights of each SNP locus. βi This system provides foundational data for calculating polygenic risk scores (PRS). Weights are determined based on large-sample association analysis, accurately reflecting the contribution of each SNP locus to the genetic risk of VKH disease. The calculation module combines genotype coding values ​​with effect weights using a pre-defined formula to quantify an individual's PRS value, achieving a quantitative assessment of genetic risk. The assessment module stratifies individual risk based on PRS values, outputting clear assessment results and providing a scientific basis for clinical decision-making and high-risk population management. The entire system is highly automated and easy to operate, effectively reducing human error and improving assessment efficiency and accuracy.

[0033] In some specific examples, the effect weights of each SNP locus in the aforementioned VKH disease genetic risk assessment system are... βi The results are shown in Table 1 below.

[0034] It should be noted that the effect weights of the above-mentioned SNP sites are... βi The PRS value is calculated using a large-sample VKH case-control study combined with a regression analysis model. It accurately reflects the contribution of each SNP locus to the genetic risk of VKH and is the core basis for calculating the PRS value. Table 1 further clarifies the effect alleles (alleles associated with the genetic risk of VKH), reference alleles (alleles used as controls), and their corresponding values ​​for each SNP locus. βi Value, of which βi A positive value indicates that the effector allele increases an individual's genetic risk of VKH disease, and βiThe higher the value, the higher the risk contribution (e.g., rs117726495). βi =1.82, which is the site with the highest risk contribution). βi A negative value indicates that the effector allele reduces an individual's genetic risk of VKH disease, and the larger the absolute value, the stronger the protective effect (e.g., rs9271522). βi =-0.94, with the most significant protective effect).

[0035] In some specific examples, in the VKH disease genetic risk assessment system mentioned above, the coded value in the calculation module... Gi According to the additive inheritance model, when the target individual is homozygous for the effect allele at the stated SNP locus... Gi =2; when the target individual is heterozygous. Gi =1; when the target individual is homozygous for the reference allele. Gi =0.

[0036] It should be noted that the encoded value Gi The determination of the risk was made using an additive genetic model, which aligns with the polygenic inheritance characteristics of VKH disease. This model can accurately quantify the contribution of each SNP genotype to the genetic risk, ensuring the scientific validity and rationality of the PRS value calculation. The core logic of the additive genetic model is the "effect allele dosage effect," meaning that the number of effect alleles is positively correlated with the genetic risk. βi (positive value) or negative correlation ( βi (Negative value): When the effect allele is homozygous (containing 2 effect alleles), Gi =2, corresponding to the highest risk contribution (or protective contribution); when heterozygous (containing 1 effect allele), Gi =1, the risk contribution (or protective contribution) is half that of the homozygous type; when referring to the homozygous allele (containing 0 effect alleles), Gi =0, meaning there is no risk or protective contribution corresponding to this site.

[0037] In some specific examples, in the VKH disease genetic risk assessment system mentioned above, the assessment module is configured to compare the calculated PRS value with a preset threshold. If the PRS value is higher than the threshold, the result is output that the target individual has a high genetic risk of VKH disease; if the PRS value is lower than the threshold, the result is output that the target individual has a low genetic risk of VKH disease.

[0038] It should be noted that the preset threshold in this invention is determined based on the PRS value distribution of a large sample case-control population. Statistical methods are used to define high-risk and low-risk thresholds, ensuring the scientific validity and reliability of the threshold. This threshold can be flexibly adjusted according to the genetic characteristics of different populations (such as different ethnicities or regions). When the PRS value is higher than the threshold, it indicates that the individual carries more VKH disease susceptibility alleles, with a significantly higher genetic risk than the general population, requiring close monitoring, regular screening, and early intervention when necessary. When the PRS value is lower than the threshold, it indicates that the individual carries fewer susceptibility alleles, with a lower genetic risk than the general population, allowing for routine prevention and control. This determination method enables rapid screening and stratified management of high-risk groups for VKH disease, improving the targeting and efficiency of disease prevention and control, and is suitable for clinical screening, genetic counseling, and other scenarios.

[0039] In some specific examples, the threshold in the VKH disease genetic risk assessment system mentioned above is 1.14.

[0040] It should be noted that setting PRS=1.14 as the cutoff value (threshold) can achieve a sensitivity of 0.73 and a specificity of 0.88.

[0041] Fifthly, embodiments of the present invention provide a computer-readable storage medium having a computer program stored thereon, wherein the computer program, when executed by a processor, performs the following steps: (a) Obtain genotype data of each SNP locus in the SNP molecular marker combination of claim 1 for the target individual; (b) Calculate the polygenic risk score (PRS) according to the following formula: ,in, βi is The pre-determined effect weight of the i-th SNP site Gi The encoded value determined based on the genotype data; (c) Assess the genetic risk of VKH disease in target individuals based on polygenic risk scores.

[0042] It should be noted that the core function of the computer-readable storage medium in this invention is to store a computer program for VKH disease genetic risk assessment, thereby automating the assessment process and adapting to different computing devices (such as computers, servers, embedded systems of testing instruments, etc.). The three steps of program execution are logically coherent. Step (a) can interface with a data acquisition module or external testing equipment to quickly read the genotype data of 22 SNP loci of the target individual, ensuring convenient data acquisition; Step (b) follows a preset formula, combined with the stored effect weights. βi With genotype coding value GiThe system automatically calculates PRS values, avoiding errors caused by manual calculation and improving calculation efficiency and accuracy. Step (c) automatically outputs risk assessment results based on the PRS value and preset thresholds, enabling rapid assessment of genetic risk. This storage medium is reusable, portable, and deployable, and can be embedded in VKH disease genetic risk assessment systems and clinical testing equipment, promoting the automation and standardization of VKH disease genetic risk assessment, reducing manual operation costs, and improving the convenience and accessibility of assessment.

[0043] To better understand the present invention, specific examples are provided below to further illustrate the content of the present invention, but the content of the present invention is not limited to the examples below.

[0044] Example 1: Screening of key SNP sites related to VKH disease

[0045] This embodiment obtains a set of key SNP sites that are significantly associated with VKH disease through genome-wide association analysis (GWAS) and subsequent fine screening.

[0046] (1) Acquisition of research subjects and sample construction

[0047] This embodiment uses two independent queues as discovery samples: Cohort 1: 774 VKH patients and 4492 healthy controls; all cases met the diagnostic criteria for VKH by clinical diagnosis, and the controls were healthy individuals without a history of VKH; peripheral blood samples were collected for genotyping.

[0048] Cohort 2: 2634 VKH patients and 10912 healthy controls. The case and control criteria were the same as in Cohort 1.

[0049] (2) Genotyping and Sample Quality Control

[0050] Cohort 1 used the Illumina Human Omni ZhongHua-8 chip for whole-genome genotyping; Cohort 2 used the Illumina ASAMD chip for genotyping.

[0051] Sample quality control was performed, and the following samples were excluded: samples with a genotyping detection rate of less than 98%; samples with kinship (PI_HAT > 0.25); and samples whose genetic sex was inconsistent with clinical information. After quality control, cohort 1 retained 608 patients and 4417 controls; cohort 2 retained 2417 patients and 10055 controls.

[0052] (3) Quality control of genetic loci

[0053] The obtained SNP data underwent quality control, and the following loci were removed: loci with a detection rate below 98%; loci with a minor allele frequency (MAF) of less than 1%; and loci that significantly deviated from Hardy-Weinberg equilibrium in healthy controls (P < 1 × 10⁻⁶). -4 The loci are located on the sex chromosomes. After quality control, cohort one retained 370,577 loci, and cohort two retained 425,907 loci.

[0054] (4) Genotype filling

[0055] Genotyping was performed based on the East Asian population reference genome (IMPUTE5 v1.2.0, 1000 Genomes Project East Asian (EAS), INFO > 0.8).

[0056] (5) Genome-wide association analysis

[0057] After adjusting for age, sex, and population structure factors, an additive genetic model was used to statistically analyze the association between each genetic locus and VKH disease, screening for genome-wide significance (P < 5 × 10⁻⁶). -8 ) genetic susceptibility loci.

[0058] (6) Screening of key genetic susceptibility loci and meta-analysis

[0059] For HLA regions, stepwise conditional regression analysis was used to screen for mutually independent genetic loci: the starting signal was selected based on the minimum P-value or the maximum effect value (if P values ​​were tied, the one with the largest OR was selected); this signal was introduced into the regression model as a covariate (i.e., the "condition" was above it) for conditional analysis; the process was iterated until no significant signal was found at the remaining loci, and mutually independent HLA alleles and SNPs were screened.

[0060] For non-HLA regions, linkage disequilibrium analysis was used to screen for independent genetic loci that were significantly associated with VKH disease. Loci with a filler confidence level higher than a preset threshold were retained: 1) Callrate < 98% (cases or controls were excluded if either side did not meet the threshold); 2) MAF < 1% (low small allele frequency was not conducive to robust statistics); 3) the Hardy–Weinberg equilibrium in the control group was severely deviated, P < 1 × 10⁻⁶. -4 ;4) Sites where the difference between the MAF and 1KGEAS data in the control group is >20% (suggesting possible typing errors or systematic bias).

[0061] Meta-analysis was performed on the association analysis results obtained at different stages, retaining only SNPs present in both stages, and using Cochran's Q and I metric. 2 Statistics evaluate heterogeneity; if I2 ≤30% indicates that the two queues are basically the same, and the Mantel–Haenszel model should be used; if I 2 If the percentage is greater than 30%, then a random effects model should be used.

[0062] Finally, after two-stage GWAS and meta-analysis, 22 key SNP loci significantly associated with VKH disease were screened from data of 3025 patients and 14472 controls. These included 4 HLA regional genetic loci and 18 non-HLA regional genetic loci. The specific information is shown in Table 1 below.

[0063] Table 1. Detailed information on the 22 SNP loci

[0064] Example 2: Construction and Validation of a Multigene Risk Scoring Model Based on 22 SNP Loci

[0065] Based on the 22 key SNP sites screened in Example 1, this embodiment constructs a multigene risk score (PRS) model and evaluates its risk prediction performance for VKH disease in an independent external validation cohort.

[0066] (1) Construction of a multi-gene risk scoring model

[0067] The genotype of each SNP locus was encoded using an additive genetic model: 0: homozygous reference allele; 1: heterozygous; 2: homozygous effect allele. The code for the i-th SNP locus is denoted as . Gi The effect weight corresponding to this site is βi (See Table 1). The polygenic risk score (PRS) is calculated using the following formula: .

[0068] The following example illustrates this model: Suppose that the genotype codes and corresponding contributions of an individual at 22 loci are shown in Table 2 below (partial example): Table 2. Examples of Multigene Risk Scoring Models

[0069] The PRS value of this example individual is -0.87.

[0070] (2) External verification

[0071] The performance of the PRS model described above was evaluated using an independent external validation queue.

[0072] The validation cohort included 141 patients with VKH (clinically diagnosed according to the VKH disease diagnostic criteria) and 1021 healthy controls. All validation samples were genotyped using an Illumina ASAMD chip, and quality control and genotyping were performed following the same steps as in Example 1. After obtaining genotypic data for each individual at 22 SNP loci, a risk score was calculated for each individual using the aforementioned PRS formula. The receiver operating characteristic (ROC) curve was then used to evaluate the PRS model's ability to distinguish between VKH cases and healthy controls. Results are as follows: Figure 1 As shown, the results indicate that the area under the curve (AUC) of the PRS model on the external validation dataset is 0.85, with a 95% confidence interval of 0.8104–0.8895. Furthermore, setting PRS=1.14 as the cutoff value (this invention uses the Youden Index as the threshold (cutoff value) optimization standard, defined as: J=Sensitivity + Specificity - 1. For each candidate threshold, the corresponding Youden Index value is calculated, and the threshold that maximizes the Youden Index is selected as the optimal classification threshold. This threshold achieves the best balance between sensitivity and specificity, thus realizing the optimal differentiation of VKH disease risk), the sensitivity can reach 0.73, and the specificity can reach 0.88.

[0073] The above results indicate that the multigene risk scoring model constructed based on the 22 SNP loci maintains good predictive performance in independent external validation populations, can effectively distinguish VKH disease patients from healthy controls, has good generalization ability, and can be used for quantitative assessment and risk stratification of VKH disease genetic risk.

[0074] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications or substitutions should be covered within the scope of the claims of the present invention.

Claims

1. A combination of SNP molecular markers for assessing the genetic risk of VKH disease, characterized in that, Information on SNP molecular marker combinations is shown below: 。 2. A reagent or kit for assessing the genetic risk of VKH disease, characterized in that, The reagent or kit contains reagents for detecting the SNP molecular marker combination of claim 1.

3. The reagent or kit according to claim 2, characterized in that, Reagents used to detect SNP molecular marker combinations include: Primer pairs that specifically amplify SNP sites; and / or Probes that specifically bind to SNP sites.

4. The reagent or kit according to claim 2 or 3, characterized in that, The reagent or kit may also contain one or more of the following components: PCR reaction solution, DNA polymerase, dNTPs, positive control or negative control.

5. The use of the reagent for detecting the SNP molecular marker combination of claim 1 in the preparation of reagents or kits for assessing the genetic risk of VKH disease.

6. A VKH disease genetic risk assessment system, characterized in that, include: The data acquisition module is used to acquire the genotype data of each SNP locus in the SNP molecular marker combination of claim 1 for the target individual; The storage module stores the pre-determined effect weights for each SNP locus. βi ; The calculation module is used to calculate the polygenic risk score (PRS) according to the following formula: ,in, Gi The encoded value determined based on the genotype data; An assessment module is used to assess the genetic risk of VKH disease in the target individual based on the polygenic risk score.

7. The VKH disease genetic risk assessment system according to claim 6, characterized in that, Effect weights of each SNP site βi They are shown below: 。 8. The VKH disease genetic risk assessment system according to claim 6 or 7, characterized in that, In the calculation module, the encoded value Gi Determined according to the additive inheritance model: When the target individual is homozygous for the effector allele at the stated SNP locus Gi =2; When the target individual is heterozygous Gi =1; When the target individual is homozygous for the reference allele Gi =0.

9. The VKH disease genetic risk assessment system according to claim 6 or 7, characterized in that, The assessment module is configured to compare the calculated PRS value with a preset threshold. If the PRS value is higher than the threshold, the result is output that the target individual has a high genetic risk of VKH disease; if the PRS value is lower than the threshold, the result is output that the target individual has a low genetic risk of VKH disease.

10. A computer-readable storage medium having a computer program stored thereon, characterized in that, When the program is executed by the processor, it performs the following steps: (a) Obtain genotype data of each SNP locus in the SNP molecular marker combination of claim 1 for the target individual; (b) Calculate the polygenic risk score (PRS) according to the following formula: ,in, βi is The pre-determined effect weight of the i-th SNP site Gi The encoded value determined based on the genotype data; (c) Assess the genetic risk of VKH disease in target individuals based on polygenic risk scores.

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