Evaluating reported candidate gene associations with polycystic ovary syndrome

Abstract

Objective: To replicate variants in candidate genes associated with polycystic ovary syndrome (PCOS) in a population of European women with PCOS and control subjects.

Design: Case-control association analysis and meta-analysis.

Setting: Major academic hospital.

Patient(s): Women of European ancestry with PCOS (n = 525) and controls (n = 472), aged 18-45 years.

Intervention(s): Variants previously associated with PCOS in candidate gene studies were genotyped (n = 39). Metabolic, reproductive, and anthropomorphic parameters were examined as a function of the candidate variants. All genetic association analyses were adjusted for age, body mass index, and ancestry and were reported after correction for multiple testing.

Main outcome measure(s): Association of candidate gene variants with PCOS.

Result(s): Three variants, rs3797179 (SRD5A1), rs12473543 (POMC), and rs1501299 (ADIPOQ), were nominally associated with PCOS. However, they did not remain significant after correction for multiple testing, and none of the variants replicated in a sufficiently powered meta-analysis. Variants in the FBN3 gene (rs17202517 and rs73503752) were associated with smaller waist circumferences, and variant rs727428 in the SHBG gene was associated with lower sex hormone-binding globulin levels.

Conclusion(s): Previously identified variants in candidate genes do not seem to be associated with PCOS risk.

Clinical trial registration number: NCT00166569.