In the largest genetic analysis of polycystic ovary syndrome (PCOS) performed to date, an international consortium, including researchers at the Icahn School of Medicine at Mount Sinai, conducted a whole genome association study to identify common genetic architecture for different diagnostic criteria used to define the syndrome. The results were published in the journal PLOS Genetics.
PCOS is among the most common endocrine disorders in reproductive-age women; it is a leading cause of infertility and type 2 diabetes. The origin of PCOS is unknown. It is currently diagnosed based on different sets of clinical criteria, which is controversial and possibly less accurate.
The researchers explored the genetic basis of PCOS by conducting a meta-analysis of seven studies involving more than 10,000 women with PCOS and 100,000 controls of European ancestry. These studies included 2,540 patients diagnosed using the National Institutes of Health criteria (high testosterone and irregular menstrual cycles); 2,669 patients using the Rotterdam criteria (high egg production); and 5,184 self-reported cases from the personal genetics company 23andMe.
With the benefit of this sample size, researchers were able to identify 14 gene variants that were associated with PCOS, including three that were identified for the first time. All the new genetic variants plausibly linked to both metabolic and reproductive features of PCOS.
“This study also indicates the enormous power of genome-wide association studies to provide insight into the disease. For the first time, we’re making real progress on understanding the causal pathways leading to PCOS and the diseases that are genetically related to it,” said Andrea Dunaif, MD, Chief of the Hilda and J. Lester Gabrilove Division of Endocrinology, Diabetes, and Bone Disease at the Icahn School of Medicine at Mount Sinai, and one of the senior authors of the study. Ultimately, Dr. Dunaif hopes that these biologic insights will enable the development of novel therapies for PCOS.