Molecular Genetics of Polycystic Ovary Syndrome: An Update

Polycystic ovary syndrome (PCOS) is a complex genetic disorder caused by interplay between several ‘susceptibility’ genes and environment factors. In the past few years, numerous studies of genomics and transcriptomics attempted to discover genes affecting PCOS. Pre-genome wide association study (GWAS) plays a stepping stone effect on the progress of PCOS, even though most of the strongest associations are for loci rather than functional variants. A trend towards large-scale GWAS has succeeded in identifying many additional novel PCOS loci. Most of the PCOS-associated regions are shared with other diseases or symptoms, as well as with metabolism, inflammation or insulin signaling-related traits, or cancer. Moreover, susceptibility genes for early diagnosis of PCOS are expected to offer the prevention of long-term risk of obesity, cardiovascular disease, and type 2 diabetes (T2DM) as well. Furthermore, considerable advanced new technical approaches such as GWAS and next-generation sequencing will provide new opportunities in the molecular analysis of PCOS, which can, in the long term, lead to new therapeutic treatments for the disorder. The present review discusses heterogeneous clinical manifestations of PCOS, controversies surrounding the diagnosis of PCOS, and the recent findings of pre-GWAS and GWAS studies on PCOS, highlighting the relevant candidate gene families and their potential functional pathways relevant for PCOS.