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

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 2018 Dec 26

PMID 30583798

Citations 48

Authors

Jonas Bovijn

Leigh Jackson

Jenny Censin

Chia-Yen Chen

Triin Laisk

Samantha Laber

Teresa Ferreira

Sara L Pulit

Craig A Glastonbury

Jordan W Smoller

Jamie W Harrison

Katherine S Ruth

Robin N Beaumont

Samuel E Jones

Jessica Tyrrell

Andrew R Wood

Michael N Weedon

Reedik Magi

Benjamin Neale

Cecilia M Lindgren

Anna Murray

Michael V Holmes

Affiliations

Soon will be listed here.

Abstract

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), 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.

Citing Articles

Identification of Systemic Drug Targets for Anti-cavernous Fibrosis in the Treatment of Erectile Dysfunction, Guided by Genome-Wide Mendelian Randomization.

Chen Z, Wang Q, Zhang L, Qiu J, Zeng Y, Kuang H Am J Mens Health. 2025; 19(2):15579883251323187.

PMID: 40077914 PMC: 11905014. DOI: 10.1177/15579883251323187.

Exploring the causal associations of gout and serum uric acid levels on erectile dysfunction: A Mendelian randomization study.

Zhang J, Ji L Medicine (Baltimore). 2025; 104(8):e41679.

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Genetically Proxied Phosphodiesterase Type 5 (PDE5) Inhibition and Risk of Dementia: A Drug Target Mendelian Randomization Study.

Brennan S, Tinworth A Mol Neurobiol. 2025; .

PMID: 39951190 DOI: 10.1007/s12035-025-04732-9.

A Mendelian randomization study on associations between plasma lipidome, circulating inflammatory proteins, and erectile dysfunction.

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The associations among platelet count, mean platelet volume, and erectile dysfunction: an observational and Mendelian randomization study.

Peng J, An J, Chen Y, Zhou J, Xiang B Sex Med. 2025; 12(6):qfae093.

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