GWAS Identifies Risk Locus for Erectile Dysfunction and Implicates Hypothalamic Neurobiology and Diabetes in Etiology

Published on Jan 3, 2019in American Journal of Human Genetics10.502
· DOI :10.1016/J.AJHG.2018.11.004
Jonas Bovijn5
Estimated H-index: 5
(University of Oxford),
Leigh Jackson17
Estimated H-index: 17
(University of Exeter)
+ 19 AuthorsMichael V. Holmes52
Estimated H-index: 52
(NIHR: National Institute for Health Research)
Erectile dysfunction (ED) is a common condition affecting more than 20% of men over 60 years, yet little is known about its genetic architecture. We performed a genome-wide association study of ED in 6,175 case subjects among 223,805 European men and identified one locus at 6q16.3 (lead variant rs57989773, OR 1.20 per C-allele; p = 5.71 × 10 −14 ), located between MCHR2 and SIM1 . In silico analysis suggests SIM1 to confer ED risk through hypothalamic dysregulation. Mendelian randomization provides evidence that genetic risk of type 2 diabetes mellitus is a cause of ED (OR 1.11 per 1-log unit higher risk of type 2 diabetes). These findings provide insights into the biological underpinnings and the causes of ED and may help prioritize the development of future therapies for this common disorder.
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