Genetics of Polycystic Ovary Syndrome

The document from March 2, 2016, provides a comprehensive analysis of the genetic factors involved in Polycystic Ovary Syndrome (PCOS). It reports a heritability estimate of 70% for PCOS from twin studies, indicating a significant genetic component, which is often influenced by weight gain. The document critiques the candidate gene approach due to inconsistent results and small study sizes, while highlighting the potential of Genome-Wide Association Studies (GWAS) that have identified genetic variants related to gonadotrophin secretion and action. It also points to the role of epigenetic factors in PCOS heritability. A UK-based study involving over 170 women with PCOS and 100 controls found increased 5α-reductase activity in PCOS patients, although genetic associations with the SRD5A gene were limited. GWAS have identified 16 significant loci associated with PCOS, and a specific GWAS with over 980 women with PCOS and over 2900 controls found three genome-wide significant loci. Despite these findings, much of the heritability of PCOS remains unexplained, underscoring the need for further research to identify additional genetic and epigenetic factors to better understand and treat PCOS. The document also notes the lack of genetic evidence for β-cell dysfunction in PCOS, despite its epidemiological overlap with type 2 diabetes, and the absence of association between certain genes like TCF7L2 or KCNJ11 and PCOS. It emphasizes the complexity of PCOS genetics and the need for larger, more powerful studies for replication and validation of results.