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Polycystic ovary syndrome is characterized by reproductive and metabolic disturbances throughout the female lifespan. Therefore, this study aimed to determine whether genome-wide association studies (GWAS)-identified risk variants for PCOS could confer risk of metabolic syndrome (MS) or insulin resistance (IR). Fifteen independent SNPs mapping to 11 GWAS loci genotyped in a total of 2,082 Han Chinese women independent of previous GWAS and phenotype-genotype correlations were assessed. The CC group for rs12478601 in  THADA  was associated with decreased rate of MS after adjustment for age (23.2 vs. 27%,  P  = 0.042, OR = 0.81). Using a dominant model, the GG+AG group for rs2059807 in  INSR  was associated with increased risk of MS after adjustment for age (26.8 vs. 22.5%,  P  = 0.023, OR = 1.27). The GG + GT group for rs4784165 in  TOX3  was found to be associated with an increased rate of IR after adjustment for age and BMI(53.3 vs. 48.5%,  P  = 0.027, OR = 1.27). The GG+AG group for rs2479106 in  DENND1A  was associated with a decreased rate of IR (48.3 vs. 53.6%, adjusted  P  = 0.039, OR = 0.80). After exclusion of PCOS cases with a family history of diabetes, hypertension, or dyslipidemia, the phenotype-genotype correlations between the genes  INSR  and  TOX3  and MS or IR were still significant ( P  < 0.05). Three SNPs (rs13429458 in  THADA , rs10818854 in  DENND1A , and rs2059807 in  INSR ) were significantly associated with IR; however, their association was not significant after adjustment for age and BMI. This genotype-phenotype study thus provides clues that  THADA, INSR, TOX3 , and  DENND1A  play a role in PCOS possibly through a metabolic disorder-related pathway.

PCOS-GWAS Susceptibility Variants in THADA, INSR, TOX3, and DENND1A Are Associated With Metabolic Syndrome or Insulin Resistance in Women With PCOS