First genetic risk factor found for erectile dysfunction
In a specific area of the genome, variations were associated with a 26 percent increased risk of the sexually limiting condition.
Barbara Clements, 206-221-6706 or email@example.com
For the first time, a team of researchers has found a specific place in the human genome where variations can raise a person’s risk of erectile dysfunction. The study, Genetic variation in the SIM1 locus is associated with erectile dysfunction, was published Oct. 8 in the journal Proceedings of the National Academy of Sciences.
“This study points to a new research direction for erectile dysfunction that could help us identify other key genetic variants that trigger the disease and could lead to investigations to better understand the precise mechanisms by which they operate,” said Hunter Wessells, chair of urology at the University of Washington School of Medicine and one of the study’s principal investigators. “Hopefully, this will translate into better treatments and, importantly, prevention approaches for the men and their partners who often suffer silently with this condition.
“This is the first time there’s ever been any strong evidence that there’s actually a genetic component to erectile dysfunction independent of all those other possible causes. This changes everything,” Wessells said.
Erectile dysfunction, the inability to obtain and maintain an erection sufficient for sexual activity, is a common and costly condition of men. It primarly affects middle-aged and older men. The disease is linked to many causes, including neurological, hormonal and vascular factors. New therapeutics are needed because about half of all men don’t respond to available pharmaceutical treatments.
The new study found that variations in a specific place in the genome, near the SIM1 gene, are significantly associated with an increased risk of erectile dysfunction. The researchers ruled out that the risk was due to other known risk factors for erectile dysfunction, such as body mass index, or differences in how men describe their erectile dysfunction. By demonstrating a biological role for the genetic location in regulating sexual function, the study strongly suggested that these variations can cause erectile dysfunction.
The two-year study points to the potential of targeting variations in the SIM1 locus on the genome in developing new erectile dysfunction treatments.
"We found the association so strong, that it gave us confidence this wasn't by chance," Wessells said of the genetic connection.
Genetics had been suspected in about one-third of erectile dysfunction cases, but researchers had failed to make an association with any specific genomic locations until now. The study found that variations in the SIM1 locus were associated with a 26 percent increased risk of erectile dysfunction. Replicating the association in the U.K. Biobank sample helped confirm the findings.
The research was conducted a a genome-wide association study in two large, diverse cohorts. The first included 36,648 men from the Genetic Epidemiology Research on Adult Health and Aging cohort, or GERA. Those findings were then verified in a cohort of 222,358 men from the UK Biobank. The existence of these genetic banks finally made this research possible, said Wessells, who has been studying this topic for 15 years.
An actual clinical treatment for erectile dysfunction, based on these findings, is years in the future. The next step, Wessells said, it to take these results, and test them against an even larger database, and against laboratory computer models.
Erectile dysfunction has been difficult to study in part because of the differences in how patients report their symptoms. To overcome this challenge, the study looked to see whether the SIM1 locus was a risk factor when considering the various ways men told their doctors about their sexual problems. The study found that this location was stil a risk factor for erectile dysfunction, whether the disorder was defined through clinical diagnoses, prescriptions history, or self-reported by study participants.
The UW School of Medicine, Kaiser Permanente Northern California, UCSF and the University of Utah collaborated on the study. Co-authors from the UW School of Medicine included Melody R. Palmer and Gail Jarvik. Co-authors on the study from the Kaiser Division of Research include Jie Yin, Jun Shan and Khanh K. Thai. Co-authors from the University of California, San Francisco, include Navneet Matharu, Thomas J. Hoffmann, Xujia Zhou and Nadav Ahituv. Co-author James M. Hotaling is from the University of Utah School of Medicine.
This research was supported in part by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK104764). The study also was funded by the National Institutes of Health (RC2 AG036607), the Robert Wood Johnson Foundation, the Wayne and Gladys Valley Foundation, The Ellison Medical Foundation, and the Kaiser Permanente Community Benefits Program.
The Kaiser Permanente Research Bank provided data from its collection, which includes the Kaiser Permanente Research Program on Genes, Environment, and Health, and the GERA data.
Access to data used in this study may be obtained by application to the KPRB via ResearchBankAccess@kp.org.