Extensive genetic analysis suggests that at least half of women with polycystic ovary syndrome (PCOS) could have rare variants of a common gene involved in hormone production.

PCOS is an incurable and poorly understood hormonal disorder in women of reproductive age and is a leading cause of both infertility and type 2 diabetes. It’s unknown what causes the disorder and there is no cure, but understanding the genetic mechanisms involved could help inform future therapies and diagnoses, say the authors of a new study published in The Journal of Clinical Endocrinology & Metabolism.

By sequencing the DNA of members of 62 families with a history of PCOS, the team found that rare variants of a gene responsible for regulating testosterone called DENND1A were present in at least half of participants, suggesting susceptibility to the condition could be inherited. 

“Our best understanding now is this strong genetic susceptibility of PCOS,” lead researcher Andrea Dunaif told IFLScience in an interview. “It’s very, very common and that’s why we see so much of it. The hope would be that with genetic testing we may be able to identify high-risk people and start measures early.”

Reproductive and metabolic hormone levels often found in cases of PCOS were associated with rare genetic variants in DENND1A, which is particularly relevant as one of the key symptoms of the disorder is increased ovarian testosterone productivity. Dunaif says that understanding the genetic factors that contribute to PCOS could help predict who is going to get PCOS or a certain subset of it, as well as lead to targeted personalized therapies.

“When we understand the genetic pathways that are involved, we can develop drugs to target them. It may be that the gene variants that we’re discovering, which are mainly in the parts of DENND1A, regulate the amount of it that is produced in tissues and maybe some of the structure,” she said. “If we understand that, then we may be able to come up with ways to alter the increase in DENND1A activity that happens in PCOS and treat the disease itself and even cure a number of patients.”

Though promising, Denaif says such measures are still a way off. Researchers will need to spend a few years working out whether testing for DENND1A is a good predictive test, but she says that within the next decade she hopes genetic information will be used to more accurately predict PCOS.

“Whatever the reason, PCOS is exceptionally common and it is poorly understood. Many women need to see as many as four physicians before they get a diagnosis. Because we don’t know what causes it, the treatments are all symptomatic and it’s very frustrating that we don’t have a cure,” said Dunaif, noting the study is limited in that it only looked at women of European ancestry and is still a relatively small sample size.

Under the most conservative diagnostic criteria, 7 percent of reproductive-age women around the world have PCOS – but it’s expected that more than one in 10 actually suffer from the disorder.