SNPs associated with polycystic ovary syndrome, chips comprising the same and use thereof
A chip and probe set technology, applied in the field of SNP, which can solve problems such as complex interactions
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Embodiment 1
[0030] Example 1: Genome-wide correlation study
[0031] To identify the genetic susceptibility loci for PCOS in the Chinese Han population, the inventors conducted a GWA study genotyping 906,600 SNPs in 744 affected individuals (cases) and 895 controls on ANFY SNP6.0 . After QC filtering, a total of 649,264 SNPs were retained and analyzed statistically. The genome inflation factor (λ = 1.097) indicated very slight inflation due to population-stratified GWAS results, whereas MDS analysis demonstrated no apparent population basis. Initial analysis revealed 3 distinct loci (2p16.3, 2p21 and 9q33.3, including 15 SNPs) showing significant genome-wide associations (P-8 ). The most significant SNP at these loci was rs13405728 in the gene LHCGR (2p16.3) (allelic P-value=1.29×10 -8 ; odds ratio, 0.61), rs12468394 in the gene THADA (2p21) (allele P value = 3.99 × 10 -10 ; odds ratio, 0.60) and rs10986105 in the gene DENND1A (9q33.3) (allele P value = 9.78 × 10 -10 ; odds ratio, 2....
Embodiment 2
[0032] Example 2: Repeating the study
[0033] To confirm the findings of the GWAS, the inventors analyzed the 28 SNPs (which showed the strongest association in the GWAS (P-6 )) were genotyped (Table 2): Series 1 included an independent sample set of 2840 PCOS cases and 5012 controls from Han Chinese in northern China; Series 2 included an additional 498 PCOS cases from Han Chinese in central and southern China and 780 controls. In series 1 replicates, 28 of 29 SNPs were confirmed. All selected SNPs (1 SNP in the gene LHCGR, 21 SNPs in the gene THADA and 6 SNPs in the gene DENND1A) found in these susceptibility loci in GWAS were confirmed with p-values ranging from 1.18 × 10 -7 to 5.55×10 -16 . In addition, 20 SNPs were positive in the series 2 replicate study, the most significant SNP being rs13405728 in the gene LHCGR (p-value = 7.93 × 10 -7 )(Table 2).
Embodiment 3
[0034] Embodiment 3: Combination analysis
[0035] In addition to correlation testing for each replicate set, the inventors performed a combined analysis of the GWAS data using meta-analysis. The Mantel-Haenszel method was used to estimate the pooled odds ratios for all strata as a fixed effects model. After combining GWAS and replicate data, the most significant association was observed at the following SNP: rs13429458 (2p21, P meta =1.73×10 -23 , odds ratio=0.67, 95%CI:0.62-0.72), rs13405728 (2p16.3, P meta =7.55×10 -21 , odds ratio=0.71, 95%CI:0.67-0.77) and rs2479106 (9q33.3, P meta =8.12×10 -19 , odds ratio=1.34, 95%CI:1.26-1.43) (Table 2, figure 2 ). All selected SNPs in these three susceptibility loci showed significant associations (p-values ranging from 2.36 × 10 -13 to 1.73×10 -23 ). The results of the binding assay strongly support that variants in the genes LHCGR, THADA, DENND1A are associated with susceptibility to PCOS.
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