Men at Risk of Erectile Dysfunction Revealed in Breakthrough Gene Analysis

For decades, researchers studying erectile dysfunction focused on a few common risk factors: smoking, drinking, and obesity. But for some guys, going dry, quitting smoking and losing weight still doesn’t solve the problem. A new study from scientists at Kaiser Permanente Health Center in California suggests the issue underlying some erectile dysfunction (ED) cases goes far deeper than physical health. It may be written in their genes.

This team isn’t interested in finding a short-term fix for persistent ED, like drugs or metal penis implants. Their study, published in the Proceedings of the National Academy of Sciences, shifts the focus from symptoms and attempts to identify their cause, which appears to be a single area on chromosome 6 that seems to control whether or not a guy will continually struggle to get it up, even if he doesn’t have other risk factors, like high body weight or alcohol and cigarette use.

It’s a big deal, study co-author Eric Jorgenson, Ph.D., tells Inverse, because it gives researchers a place to investigate when traditional treatments for erectile dysfunction fail. “This is the first genomic location to be identified for erectile dysfunction, and, more broadly, sexual function, and, for that reason, it is exciting and new,” Jorgenson says.

“The specific region in the human genome that we identified appears to act independently of these known risk factors,” he continues, “so developing new treatments that target this new risk factor have the potential to work for the more than half of men who do not respond to current treatments or interventions.”

Their analysis of the human genome turned up a stretch of DNA that’s not quite a gene but an “enhancer” — an “on-switch” that, when bound by the right proteins, increases the likelihood that a gene will get activated. In this case, this team believes their enhancer affects a gene called SIM1, which in turn helps ensure that hormones crucial for trigger erections reach their targets in the brain.

The study, which involved data on 36,649 men from the NIH-funded Genetic Epidemiology Research in Adult Health and Aging cohort and over 222,000 men from the UK Biobank, showed that some men have a slightly different enhancer region known as the “T-risk allele.”

Men with this allele tended to struggle with sexual function more than those without this tiny change, which the team demonstrated by comparing the participants’ genetic information against data on ED incidence and demonstrating the enhancer’s role in ED in lab experiments.

In the data analysis, the team split the men into four groups ranging from those who reported “always” being able to get an erection to those who said they “never” managed to do so. Of the men who reported that they “never” were able to get hard, having this gene meant they had 1.41 higher odds of having ED than those without the gene. But more importantly, Jorgenson notes, this pattern held when they adjusted for other risk factors, like obesity.

“We know that there are other risk factors for erectile dysfunction, including smoking, obesity, diabetes, and cardiovascular disease,” he says. “What is striking about the region in the human genome that we identified is that it acts independently of these known risk factors. That is, this genetic location appears to act specifically on sexual function.”

Jorgenson’s follow-up analysis on the actual function of the enhancer on SIM1, shown by previous studies to to regulate hormones crucial to sexual function. Activation of the enhancer caused cells to express SIM1, whereas controls didn’t — which is important because it suggests scientists can start looking for cells carrying the faulty enhancer allele and narrow in on them as targets for ED treatment.

“Millions of men (and their partners) suffer from erectile dysfunction, and half of them do not respond to current treatments,” says Jorgenson. “New treatments that target this newly identified genetic risk factor have the potential to benefit them.”