Genetics of Polycystic Ovary Syndrome


Polycystic ovary syndrome (PCOS) affects reproductive‐aged women, manifesting reproductive and hyperandrogenic features and associated cardio‐metabolic risk factors that include increased risk for development of type 2 diabetes. Twin‐based studies have confirmed a heritability of ∼70% for PCOS, with likely oligogenic predisposition, its clinical and biochemical abnormalities often highlighted by weight gain. Much current literature on PCOS genetics is based on a candidate gene approach, with controversial and conflicting results from reporting of almost universally under‐powered studies. In recent years, this approach has been superseded by the Genome‐Wide Association Study (GWAS) with its advantage of encompassing the entire genome without any need for a priori understanding of pathophysiology. Reported GWAS in PCOS from both Chinese and European ancestry have revealed novel insight that implicate genetic variants influencing secretion and action of gonadotrophins in susceptibility for development of this condition. Epigenetic factors probably also play an important role in the heritability of PCOS.

Key Concepts

  • PCOS is an oligogenic condition with a heritability of ∼70%.
  • PCOS is characterised by reproductive and hyperandrogenic features.
  • Genetics studies in PCOS are limited by the heterogeneity of the condition, the inherent reduced fertility and difficulty with accurate retrospective diagnosis in postmenopausal women.
  • Existing candidate gene studies implicate variants within FTO (through effects on fat mass) and variants that influence steroidogenesis (such as 5α‐reductase activity) in possible susceptibility for development of PCOS.
  • Genome‐wide association studies (GWASs) on Chinese and European populations have identified loci that implicate gonadotrophin secretion (including FSHB) in susceptibility for development of PCOS.
  • Loci identified from GWAS in PCOS only account for a small proportion of the overall heritability of PCOS. Rarer, yet to be identified, genetic variants with large effects may yet play a part but it is also likely that other factors, such as epigenetics, may contribute to the remainder of this known heritability.

Keywords: polycystic ovary syndrome; genetics; obesity; candidate gene study; genome‐wide association study


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Further Reading

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Xu Y , Li Z , Ai F , et al. (2015) Systematic evaluation of genetic variants for polycystic ovary syndrome in a chinese population. PLoS ONE 10 (10): e0140695.

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Barber, Thomas M, and Stephen, Franks(Mar 2016) Genetics of Polycystic Ovary Syndrome. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0026529]