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

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record Full summary statistics of the erectile dysfunction genome-wide meta-analysis are available at the following URL: http://www.geenivaramu.ee/tools/ED_AJHG_Bovijn_et_al_2018.gz and at the LD Hub GWAShare Center at the following URL: http://ldsc.broadinstitute.org/gwashare/.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.Novo NordiskMedical Research CouncilBritish Heart Foundation Intermediate Clinical Research FellowshipLi Ka Shing FoundationWT-SSI/John Fell fundsOxfordWidenlifeNIHNational Institute for Health Research Oxford Biomedical Research Centr