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GWAS identifies novel risk locus for erectile dysfunction and implicates hypothalamic neurobiology and diabetes in etiology

Jonas Bovijn, Leigh Jackson, Jenny Censin, Chia-Yen Chen, Triin Laisk-Podar, Samantha Laber, Teresa Ferreira, Craig Glastonbury, Jordan Smoller, Jamie W Harrison, Katherine S Ruth, Robin N Beaumont, Samuel E Jones, Jessica Tyrrell, Andrew R Wood, Michael N Weedon, Reedik Mägi, Benjamin Neale, Cecilia M Lindgren, Anna Murray, Michael V Holmes
doi: https://doi.org/10.1101/283002
Jonas Bovijn
1Big Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LF, UK
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Leigh Jackson
2Institute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK
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Jenny Censin
1Big Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LF, UK
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Chia-Yen Chen
3Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114 USA
4Psychiatric & Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA
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Triin Laisk-Podar
5Estonian Genome Center, Institute of genomics, University of Tartu, Tartu 51010, Estonia
6Department of Obstetrics and Gynecology, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia
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Samantha Laber
1Big Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LF, UK
7The Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, UK
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Teresa Ferreira
8Li Ka Shing Centre for Health Information and Discovery, Big Data Institute, University of Oxford, Oxford, UK
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Craig Glastonbury
1Big Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LF, UK
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Jordan Smoller
4Psychiatric & Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA
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Jamie W Harrison
9Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK
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Katherine S Ruth
9Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK
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Robin N Beaumont
9Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK
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Samuel E Jones
9Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK
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Jessica Tyrrell
9Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK
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Andrew R Wood
9Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK
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Michael N Weedon
9Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK
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Reedik Mägi
5Estonian Genome Center, Institute of genomics, University of Tartu, Tartu 51010, Estonia
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Benjamin Neale
3Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114 USA
4Psychiatric & Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA
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Cecilia M Lindgren
1Big Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LF, UK
7The Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, UK
8Li Ka Shing Centre for Health Information and Discovery, Big Data Institute, University of Oxford, Oxford, UK
10National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospital, Old Road, Oxford OX3 7LE, UK
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  • For correspondence: celi@broadinstitute.org A.Murray@exeter.ac.uk michael.holmes@ndph.ox.ac.uk
Anna Murray
9Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK
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  • For correspondence: celi@broadinstitute.org A.Murray@exeter.ac.uk michael.holmes@ndph.ox.ac.uk
Michael V Holmes
10National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospital, Old Road, Oxford OX3 7LE, UK
11Clinical 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
12Medical Research Council Population Health Research Unit at the University of Oxford, Nuffield Department of Population Health, University of Oxford, UK
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  • For correspondence: celi@broadinstitute.org A.Murray@exeter.ac.uk michael.holmes@ndph.ox.ac.uk
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Abstract

GWAS of erectile dysfunction (ED) in 6,175 cases among 223,805 European men identified one new 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 indicates genetic risk of type 2 diabetes causes ED. Our findings provide novel insights into the biological underpinnings of ED.

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Posted March 15, 2018.
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GWAS identifies novel risk locus for erectile dysfunction and implicates hypothalamic neurobiology and diabetes in etiology
Jonas Bovijn, Leigh Jackson, Jenny Censin, Chia-Yen Chen, Triin Laisk-Podar, Samantha Laber, Teresa Ferreira, Craig Glastonbury, Jordan Smoller, Jamie W Harrison, Katherine S Ruth, Robin N Beaumont, Samuel E Jones, Jessica Tyrrell, Andrew R Wood, Michael N Weedon, Reedik Mägi, Benjamin Neale, Cecilia M Lindgren, Anna Murray, Michael V Holmes
bioRxiv 283002; doi: https://doi.org/10.1101/283002
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GWAS identifies novel risk locus for erectile dysfunction and implicates hypothalamic neurobiology and diabetes in etiology
Jonas Bovijn, Leigh Jackson, Jenny Censin, Chia-Yen Chen, Triin Laisk-Podar, Samantha Laber, Teresa Ferreira, Craig Glastonbury, Jordan Smoller, Jamie W Harrison, Katherine S Ruth, Robin N Beaumont, Samuel E Jones, Jessica Tyrrell, Andrew R Wood, Michael N Weedon, Reedik Mägi, Benjamin Neale, Cecilia M Lindgren, Anna Murray, Michael V Holmes
bioRxiv 283002; doi: https://doi.org/10.1101/283002

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