Genetic basis of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is associated with obesity and manifests with reproductive, hyperandrogenic and metabolic features. Although the etiology of PCOS is complex and incompletely understood, genetics plays an important role (heritability: ∼70%). Potential problems with studying the genetics of PCOS include the heterogeneity of the condition and associated sub-fertility. A candidate gene approach has been used in over 70 published studies on PCOS, most of which have been inadequately powered to detect a statistically meaningful association. Furthermore, these studies often fail to replicate prior published studies on the same candidate gene in different populations. The first genome-sequence variant (identified from a genome-wide association study in subjects with Type 2 diabetes mellitus) to be studied in PCOS (FTO gene) has been shown by our group to associate with susceptibility for the development of PCOS. This is the first genetic corroboration of a link between PCOS and obesity. Future directions include a genome-wide association study in PCOS.