Genetic factors account for about 30 percent of the risk for erectile dysfunction, twin studies have indicated, yet until now, no specific loci had been identified. In a study published this week (October 8) in PNAS, researchers have, through genome-wide association studies (GWAS), found such a risk factor at a region near a gene called SIM1, which they call the SIM1 locus.
“Identifying this SIM1 locus as a risk factor for erectile dysfunction is a big deal because it provides the long sought-after proof that there is a genetic component to the disease,” lead author Eric Jorgenson, a researcher at Kaiser Permanente Northern California, says in a press release. “Identifying the first genetic risk factor for erectile dysfunction is an exciting discovery because it opens the door for investigations into new, genetic-based therapies.”
The newly identified risk factor is a single-nucleotide polymorphism (SNP) on chromosome 6. Having a thymine (T) nucleotide at this position increases the risk of erectile dysfunction by around 25 percent, the researchers found, after taking into account other risk factors for the disorder.
“We know that there are other risk factors for erectile dysfunction, including smoking, obesity, diabetes, and cardiovascular disease,” Jorgenson tells Newsweek. “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 and colleagues identified the locus through a GWAS of 36,649 men from a Kaiser Permanente database. Once they identified the spot on chromosome 6 that seemed to be linked with erectile dysfunction, they then confirmed the association in data from 222,358 men from the UK Biobank. The region of interest contained several SNPs but only one was evolutionarily conserved, which is why they focused on it, the authors write in their paper.
SIM1 encodes a transcription factor involved in both sexual function and body weight regulation, and the authors note that several lines of evidence suggest that the SIM1 locus is involved in regulating the gene. The region that includes the risk factor physically interacts with the SIM1 promoter, the researchers found. Results from the ENCODE project, which endeavors to identify various functional elements of the human genome, point to the locus as a likely enhancer, and lab tests confirmed that hypothesis, namely, that the T allele boosts the activity of an enhancer regulating SIM1, the authors write.
“The next step is to find out how this location in the genome affects the risk of erectile dysfunction,” Jorgenson tells Newsweek.