Dr. Eric Jorgenson,
PhD, a Research Scientist at Kaiser Permanente Northern California's Division
of Research and the lead author of the study said: "
"Identifying the first genetic risk factor for ED is an exciting discovery
because it opens the door for investigations into new, genetic-based
performed a genome-wide association study in two large and diverse cohorts in
order to find a genetic risk factor that could be responsible for ED.
- The first
cohort was the Genetic Epidemiology Research on Adult Health and Aging
(GERA) cohort, which included 36,648 men. This cohort is a part of the
Kaiser Permanente Research Bank, which includes bio-specimens from over
- The second
cohort was the UK Biobank, which included 222,358 men. This second
cohort was used to verify the responses of the GERA cohort to a structured
questionnaire that was aimed at assessing the condition of these
The study found
that variations in the SIM1 gene locus accounted for 26 percent increased risk
of ED. Importantly, this risk excluded other causes of ED. The findings were
confirmed by the UK Biobank cohort.
Dr. Stephen Van Den
Eeden, PhD, a Research Scientist at the Kaiser Permanente Northern California's
Division of Research and the senior author of the study, said: "This
significant advance in our understanding of ED is made possible by the unique
ability of the Kaiser Permanente Research Bank to link detailed questionnaires,
electronic health records, and genetic data on such a large population."
The study confirmed
that the SIM1 locus was indeed a risk factor for ED,
disorder was established based on prescribing history, clinical diagnosis or
role of this ED locus
was established based on the function of the SIM1
gene, which is a component of a signaling pathway that plays a major role in
the regulation of body weight and sexual function.
ED risk locus was found to interact with the promoter of the SIM1 gene,
which in turn
alters the function of the enhancer, sometimes referred to as the master gene
The study suggests
that since the ED risk locus shows an enhancer activity and interacts with the
SIM1 promoter, it is very likely that it causes the differential expression of
the SIM1 gene, turning it "on" or "off" as and when required, just like a light
highlights the fact that the SIM1 locus could be a potential target
for the development of new therapeutic strategies for ED
. This is
particularly important, since almost half of all men suffering from ED don't
respond to currently available medications.
Wessells, MD, Chair of Urology at the University of Washington School of
Medicine, a co-author and one of the principal investigators of the study,
said: "This study points to a new research direction for ED that could help us
identify other key genetic variants that trigger the disease and lead to
investigations to better understand the precise mechanisms by which they
operate." He added: "Hopefully, this will translate into better treatments and,
importantly, prevention approaches for the men and their partners who often
suffer silently with this condition."
- Genome: The
complete set of genes or genetic material present in a cell or organism.
- Cohort: A
group of people with a shared characteristic.
- Enhancer: A
short region of DNA to which proteins bind to increase the transcription
of a particular gene.
- Promoter: A
region of DNA that initiates transcription of a particular gene.
- First Genetic Risk Factor for Erectile Dysfunction Identified - (https://share.kaiserpermanente.org/article/first-genetic-risk-factor-for-erectile-dysfunction-identified/)
- Erectile Dysfunction in the Elderly Male - (https://www.ncbi.nlm.nih.gov/pubmed/28861293)