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Am J Hum Genet. 2019 Jan 3;104(1):157-163. doi: 10.1016/j.ajhg.2018.11.004. Epub 2018 Dec 21.

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

Author information

1
Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7LF, UK; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK. Electronic address: jbovijn@well.ox.ac.uk.
2
Institute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Exeter EX2 5DW, UK.
3
Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7LF, UK; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
4
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Psychiatric & Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
5
Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu 51010, Estonia; Department of Obstetrics and Gynecology, Institute of Clinical Medicine, University of Tartu, Tartu 50406, Estonia.
6
Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7LF, UK.
7
Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7LF, UK; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA; Department of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
8
Psychiatric & Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
9
Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX2 5DW, UK.
10
Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu 51010, Estonia.
11
Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7LF, UK; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA.
12
Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX2 5DW, UK. Electronic address: a.murray@exeter.ac.uk.
13
National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospital, Old Road, Oxford OX3 7LE, UK; Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, Big Data Institute Building, Roosevelt Drive, University of Oxford, Oxford OX3 7LF, UK; Medical Research Council Population Health Research Unit at the University of Oxford, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

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 × 10-14), 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.

KEYWORDS:

GWAS; Mendelian randomization; SIM1; UK biobank; diabetes; erectile dysfunction; genome-wide association; impotence; mendelian randomisation

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