Large-scale study identifies shared genetic architecture for polycystic ovary syndrome diagnosis

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 whole-genome association 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.

"One of our most important findings is simply that all the fighting that goes on in the field over which diagnostic criteria to use is unnecessary," 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. "We can be pretty broad in our diagnosis with the criteria we have and be assured we are going to find the same genetic forms of PCOS."

Additional analyses provided further insight into the biology of PCOS. There was evidence that the genetic pathways identified in this study are also linked to other conditions, including obesity, type 2 diabetes, menopause, and depression. In addition, the researchers found for the first time that there are some links to male pattern baldness. The association between PCOS and male-pattern balding is particularly intriguing since it is the first genetic evidence for shared disease biology in men. The genetic link with depression supports epidemiologic studies that have found an increased risk for depression in women with 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," added Dr. Dunaif, an international authority on the disease.

Ultimately, Dr. Dunaif hopes that these biologic insights will enable the development of novel therapies for PCOS.