Genetics of Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is an oligogenic condition, with a heritability of ∼70%. PCOS is also associated with obesity, which itself is heavily influenced by genetic variants. PCOS is inherently difficult to study genetically, and most of the current literature (>70 studies based on the candidate gene approach) is inconclusive, with many studies being underpowered resulting in inconsistencies, controversies and lack of clear consensus. A further problem is that the candidate gene approach relies upon some prior understanding of pathogenesis to determine the candidacy of the gene chosen (with >20,000 genes to choose from within the human genome). PCOS has a complex and incompletely understood pathogenesis, thereby limiting the candidate gene approach for this condition. Thankfully, this limitation is overcome through use of the genome-wide association study (GWAS), the first of which in PCOS has already been published. The GWAS does not rely upon any a priori understanding of pathogenesis, and as such holds the potential to reveal hitherto unexpected or even unknown pathogenic pathways that may be implicated in the development of PCOS. Data from future GWAS in PCOS should transform our understanding of PCOS pathogenesis, and also provide a basis on which to develop future novel therapeutic strategies.