Data mining DNA for polycystic ovary syndrome genes

Polycystic ovary syndrome (PCOS) has been passed down in many families for generations - causing reproductive and metabolic health problems for millions of women around the world. Yet, its cause remains unknown despite more than 80 years of research since the disorder was first described in 1935.

A new Northwestern Medicine genome-wide association study of PCOS - the first of its kind to focus on women of European ancestry - has provided important new insights into the underlying biology of the disorder.

Using the DNA of thousands of women and genotyping nearly 700,000 genetic markers from each individual, an international team led by investigators from Northwestern Medicine have identified two new genetic susceptibility regions that appear to be unique to European women with PCOS, as well as one region also present in Chinese women with PCOS.

Most importantly, one of these new regions contains the gene for the pituitary hormone gonadotropin, FSH (follicle stimulating hormone), providing evidence that disruption in this pathway that regulates ovarian function plays an essential role in the development of PCOS.

The study was published August 18 in the journal Nature Communications.

"Identifying the genes associated with PCOS give us clues about the biological pathways that cause the disorder," said Dr. Andrea Dunaif, senior author of the study. "Understanding these pathways can lead to new treatments and disease prevention approaches."

Dunaif is the Charles F. Kettering Professor of Endocrinology and Metabolism at Northwestern University Feinberg School of Medicine. She also is a physician at Northwestern Memorial Hospital.

"There are no FDA-approved drugs for PCOS," Dunaif said. "We can manage symptoms and improve fertility in patients but, without understanding the cause of PCOS, we cannot cure the condition."

"Large-scale genetic analyses that became possible after the mapping of the human genome allow us to investigate the entire genome for disease-causing DNA variants," she said. "This information will be critical for the development of effective treatments for PCOS and for genetic testing to identify at-risk girls before the onset of symptoms."

PCOS affects seven to 10 percent of reproductive-age women worldwide with symptoms such as increased male-pattern hair growth, weight gain, irregular periods and infertility. These symptoms are due to increased production of male hormones, in particular testosterone, by the ovary and disordered secretion of the pituitary gonadotropins, LH (luteinizing hormone) and FSH, resulting in anovulation (the absence of ovulation).

As a result of previous research from Dunaif's lab, PCOS also is associated with insulin resistance and is now recognized as a leading risk factor for type-2 diabetes in young women. Her group has been at the forefront of genetic studies of PCOS and has shown that male relatives and the children of affected women are at increased risk type 2 diabetes and reproductive problems.