Metabolic and cardiovascular genes in polycystic ovary syndrome: A candidate-wide association study (CWAS)

The role of metabolic disturbance in polycystic ovary syndrome (PCOS) has been well established, with insulin resistance and the resulting compensatory hyperinsulinemia thought to promote hyperandrogenemia. Genome-wide association studies (GWAS) have established a large number of loci for metabolic conditions such as type 2 diabetes and obesity. A subset of these loci has been investigated for a role in PCOS; these studies generally have not revealed a confirmed role for these loci in PCOS risk. However, a large scale investigation of genes related to these pathways has not previously been performed. We conducted a two stage case control association study of 121,715 single nucleotide polymorphisms (SNPs) selected to represent susceptibility loci associated with traits such as type 2 diabetes, obesity measures, lipid levels and cardiovascular function using the Cardio-Metabochip in 847 PCOS cases and 845 controls. Several hypothesis-generating associations with PCOS were observed (top SNP rs2129107, P = 3.8 × 10−6). We did not find any loci definitively associated with PCOS after strict correction for multiple testing, suggesting that cardio-metabolic loci are not major risk factors underlying the susceptibility to PCOS.

► We conducted a candidate-wide association study (CWAS) in PCOS.
► The CWAS included loci for diabetes-, atherosclerosis-, and obesity-related traits.
► Several loci manifested suggestive association with PCOS (P < 1 x 10–4).
► None of over 120,000 loci were definitively associated with PCOS.
► Susceptibility loci for cardiometabolic traits do not play a major role in PCOS.