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GWAS Identifies Risk Locus for Erectile Dysfunction and Implicates Hypothalamic Neurobiology and Diabetes in Etiology.
Bovijn, Jonas; Jackson, Leigh; Censin, Jenny; Chen, Chia-Yen; Laisk, Triin; Laber, Samantha; Ferreira, Teresa; Pulit, Sara L; Glastonbury, Craig A; Smoller, Jordan W; Harrison, Jamie W; Ruth, Katherine S; Beaumont, Robin N; Jones, Samuel E; Tyrrell, Jessica; Wood, Andrew R; Weedon, Michael N; Mägi, Reedik; Neale, Benjamin; Lindgren, Cecilia M; Murray, Anna; Holmes, Michael V.
Afiliación
  • Bovijn J; 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.
  • Jackson L; Institute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Exeter EX2 5DW, UK.
  • Censin J; 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.
  • Chen CY; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Psychiatric & Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Laisk T; 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.
  • Laber S; 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.
  • Ferreira T; Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7LF, UK.
  • Pulit SL; 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.
  • Glastonbury CA; Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7LF, UK.
  • Smoller JW; Psychiatric & Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Harrison JW; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX2 5DW, UK.
  • Ruth KS; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX2 5DW, UK.
  • Beaumont RN; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX2 5DW, UK.
  • Jones SE; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX2 5DW, UK.
  • Tyrrell J; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX2 5DW, UK.
  • Wood AR; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX2 5DW, UK.
  • Weedon MN; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX2 5DW, UK.
  • Mägi R; Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu 51010, Estonia.
  • Neale B; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Psychiatric & Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Lindgren CM; 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, Cam
  • Murray A; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX2 5DW, UK. Electronic address: a.murray@exeter.ac.uk.
  • Holmes MV; 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, Universit
Am J Hum Genet ; 104(1): 157-163, 2019 01 03.
Article en En | MEDLINE | ID: mdl-30583798
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Predisposición Genética a la Enfermedad / Diabetes Mellitus Tipo 2 / Estudio de Asociación del Genoma Completo / Hipotálamo / Disfunción Eréctil Tipo de estudio: Clinical_trials / Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Humans / Male País/Región como asunto: Europa Idioma: En Revista: Am J Hum Genet Año: 2019 Tipo del documento: Article
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Predisposición Genética a la Enfermedad / Diabetes Mellitus Tipo 2 / Estudio de Asociación del Genoma Completo / Hipotálamo / Disfunción Eréctil Tipo de estudio: Clinical_trials / Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Humans / Male País/Región como asunto: Europa Idioma: En Revista: Am J Hum Genet Año: 2019 Tipo del documento: Article