Evaluating reported candidate gene associations with polycystic ovary syndrome

Variants associated with PCOS in the previously published literature failed to replicate in this case–control association study and meta-analysis.

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Cindy Pau, M.D., Richa Saxena, Ph.D., Corrine Kolka Welt, M.D.

Volume 99, Issue 6, Pages 1774-1778, May 2013



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


Case-control association analysis and meta-analysis.


Major academic hospital


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


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, BMI and ancestry and were reported after correction for multiple testing.

Main Outcome Measure:

Association of candidate gene variants with PCOS.


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.


Previously identified variants in candidate genes do not appear to be associated with PCOS risk.

Clinical Trial Registration Number:


Read the full text at: http://www.fertstert.org/article/S0015-0282(12)02542-3/fulltext

Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders.