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The genetic architecture of type 2 diabetes.
Fuchsberger, Christian; Flannick, Jason; Teslovich, Tanya M; Mahajan, Anubha; Agarwala, Vineeta; Gaulton, Kyle J; Ma, Clement; Fontanillas, Pierre; Moutsianas, Loukas; McCarthy, Davis J; Rivas, Manuel A; Perry, John R B; Sim, Xueling; Blackwell, Thomas W; Robertson, Neil R; Rayner, N William; Cingolani, Pablo; Locke, Adam E; Tajes, Juan Fernandez; Highland, Heather M; Dupuis, Josee; Chines, Peter S; Lindgren, Cecilia M; Hartl, Christopher; Jackson, Anne U; Chen, Han; Huyghe, Jeroen R; van de Bunt, Martijn; Pearson, Richard D; Kumar, Ashish; Müller-Nurasyid, Martina; Grarup, Niels; Stringham, Heather M; Gamazon, Eric R; Lee, Jaehoon; Chen, Yuhui; Scott, Robert A; Below, Jennifer E; Chen, Peng; Huang, Jinyan; Go, Min Jin; Stitzel, Michael L; Pasko, Dorota; Parker, Stephen C J; Varga, Tibor V; Green, Todd; Beer, Nicola L; Day-Williams, Aaron G; Ferreira, Teresa; Fingerlin, Tasha.
Afiliación
  • Fuchsberger C; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
  • Flannick J; Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
  • Teslovich TM; Center for Biomedicine, European Academy of Bolzano/Bozen (EURAC), affiliated with the University of Lübeck, Bolzano, Italy.
  • Mahajan A; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
  • Agarwala V; Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.
  • Gaulton KJ; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
  • Ma C; Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Fontanillas P; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
  • Moutsianas L; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
  • McCarthy DJ; Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Rivas MA; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
  • Perry JRB; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
  • Sim X; Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Blackwell TW; Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Robertson NR; Department of Statistics, University of Oxford, Oxford, UK.
  • Rayner NW; Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Cingolani P; Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Locke AE; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
  • Tajes JF; MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
  • Highland HM; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
  • Dupuis J; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
  • Chines PS; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
  • Lindgren CM; Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Hartl C; Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Jackson AU; Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Chen H; Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Huyghe JR; Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.
  • van de Bunt M; School of Computer Science, McGill University, Montreal, Quebec, Canada.
  • Pearson RD; McGill University and Génome Québec Innovation Centre, Montreal, Quebec, Canada.
  • Kumar A; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
  • Müller-Nurasyid M; Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Grarup N; Human Genetics Center, The University of Texas Graduate School of Biomedical Sciences at Houston, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
  • Stringham HM; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
  • Gamazon ER; National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.
  • Lee J; Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
  • Chen Y; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
  • Scott RA; Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Below JE; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
  • Chen P; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
  • Huang J; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
  • Go MJ; Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA.
  • Stitzel ML; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
  • Pasko D; Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Parker SCJ; Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Varga TV; Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Green T; Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Beer NL; Chronic Disease Epidemiology, Swiss Tropical and Public Health Institute, University of Basel, Basel, Switzerland.
  • Day-Williams AG; Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
  • Ferreira T; Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universität, Munich, Germany.
  • Fingerlin T; Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.
Nature ; 536(7614): 41-47, 2016 08 04.
Article en En | MEDLINE | ID: mdl-27398621
ABSTRACT
The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Variación Genética / Predisposición Genética a la Enfermedad / Diabetes Mellitus Tipo 2 Tipo de estudio: Prognostic_studies Límite: Humans País/Región como asunto: Europa Idioma: En Revista: Nature Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Variación Genética / Predisposición Genética a la Enfermedad / Diabetes Mellitus Tipo 2 Tipo de estudio: Prognostic_studies Límite: Humans País/Región como asunto: Europa Idioma: En Revista: Nature Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos