Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility.

Autor: Wessel J; 1] Department of Epidemiology, Fairbanks School of Public Health, Indianapolis, Indiana 46202, USA [2] Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA., Chu AY; 1] Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA [2] National Heart, Lung, and Blood Institute (NHLBI) Framingham Heart Study, Framingham, Massachusetts 01702, USA., Willems SM; 1] Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam 3000 CE, The Netherlands [2] MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0SL, UK., Wang S; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA., Yaghootkar H; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK., Brody JA; 1] Cardiovascular Health Research Unit, University of Washington, Seattle, Washington 98101, USA [2] Department of Medicine, University of Washington, Seattle, Washington 98195, USA., Dauriz M; 1] Massachusetts General Hospital, General Medicine Division, Boston, Massachusetts 02114, USA [2] Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA [3] Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona Medical School and Hospital Trust of Verona, Verona 37126, Italy., Hivert MF; 1] Harvard Pilgrim Health Care Institute, Department of Population Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA [2] Division of Endocrinology and Metabolism, Department of Medicine, Université de Sherbrooke, Sherbrooke, Québec, Canada J1K 2R1 [3] Diabetes Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA., Raghavan S; 1] Massachusetts General Hospital, General Medicine Division, Boston, Massachusetts 02114, USA [2] Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA., Lipovich L; 1] Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan 48201, USA [2] Department of Neurology, Wayne State University School of Medicine, Detroit, Michigan 48202, USA., Hidalgo B; Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama 35233, USA., Fox K; 1] Department of Medicine, University of Washington, Seattle, Washington 98195, USA [2] Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA., Huffman JE; 1] National Heart, Lung, and Blood Institute (NHLBI) Framingham Heart Study, Framingham, Massachusetts 01702, USA [2] MRC Human Genetics Unit, MRC IGMM, University of Edinburgh, Edinburgh, Scotland EH4 2XU, UK., An P; Division of Statistical Genomics and Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63108, USA., Lu Y; 1] The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA [2] The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA., Rasmussen-Torvik LJ; Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA., Grarup N; The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen DK-2200, Denmark., Ehm MG; Quantitative Sciences, PCPS, GlaxoSmithKline, North Carolina 27709, USA., Li L; Quantitative Sciences, PCPS, GlaxoSmithKline, North Carolina 27709, USA., Baldridge AS; Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA., Stančáková A; Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio FI-70211, Finland., Abrol R; 1] Department of Medicine and Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA [2] Materials and Process Simulation Center, California Institute of Technology, Pasadena, California 91125, USA., Besse C; CEA, Institut de Génomique, Centre National de Génotypage, 2 Rue Gaston Crémieux, EVRY Cedex 91057, France., Boland A; CEA, Institut de Génomique, Centre National de Génotypage, 2 Rue Gaston Crémieux, EVRY Cedex 91057, France., Bork-Jensen J; The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen DK-2200, Denmark., Fornage M; Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas 77030, USA., Freitag DF; 1] The Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK [2] Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge CB1 8RN, UK., Garcia ME; Intramural Research Program, National Institute on Aging, Bethesda, Maryland 21224, USA., Guo X; Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502, USA., Hara K; 1] The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA [2] The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA., Isaacs A; Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam 3000 CE, The Netherlands., Jakobsdottir J; Icelandic Heart Association, Holtasmari 1, Kopavogur IS-201, Iceland., Lange LA; Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA., Layton JC; Indiana University, Fairbanks School of Public Health, Indianapolis, Indiana 46202, USA., Li M; Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland 21205, USA., Hua Zhao J; MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0SL, UK., Meidtner K; Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal DE-14558, Germany., Morrison AC; Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas 77225, USA., Nalls MA; Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland 20892, USA., Peters MJ; 1] Department of Internal Medicine, Erasmus University Medical Center, Rotterdam 3000 CE, The Netherlands [2] The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Leiden/Rotterdam 2300 RC, The Netherlands., Sabater-Lleal M; Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm SE-171 77, Sweden., Schurmann C; 1] The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA [2] The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA., Silveira A; Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm SE-171 77, Sweden., Smith AV; 1] Icelandic Heart Association, Holtasmari 1, Kopavogur IS-201, Iceland [2] University of Iceland, Reykjavik IS-101, Iceland., Southam L; 1] The Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK [2] Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, UK., Stoiber MH; Department of Genome Dynamics, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA., Strawbridge RJ; Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm SE-171 77, Sweden., Taylor KD; Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502, USA., Varga TV; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Skåne University Hospital, Malmö SE-205 02, Sweden., Allin KH; The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen DK-2200, Denmark., Amin N; Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam 3000 CE, The Netherlands., Aponte JL; Quantitative Sciences, PCPS, GlaxoSmithKline, North Carolina 27709, USA., Aung T; 1] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore [2] Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119228, Singapore., Barbieri C; Division of Genetics and Cell Biology, San Raffaele Research Institute, Milano 20132, Italy., Bihlmeyer NA; 1] Predoctoral Training Program in Human Genetics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Maryland 21205, USA [2] McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA., Boehnke M; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA., Bombieri C; Section of Biology and Genetics, Department of Life and Reproduction Sciences, University of Verona, Verona 37100, Italy., Bowden DW; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA., Burns SM; Diabetes Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA., Chen Y; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA., Chen YD; Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502, USA., Cheng CY; 1] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore [2] Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119228, Singapore [3] Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 119228, Singapore [4] Office of Clinical Sciences, Duke-NUS Graduate Medical School, National University of Singapore, Singapore 169857, Singapore., Correa A; Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA., Czajkowski J; Division of Statistical Genomics and Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63108, USA., Dehghan A; Department of Epidemiology, Erasmus University Medical Center, Rotterdam 3000 CE, The Netherlands., Ehret GB; 1] McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA [2] Division of Cardiology, Geneva University Hospital Geneva 1211, Switzerland., Eiriksdottir G; Icelandic Heart Association, Holtasmari 1, Kopavogur IS-201, Iceland., Escher SA; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Skåne University Hospital, Malmö SE-205 02, Sweden., Farmaki AE; Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens 17671, Greece., Frånberg M; 1] Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm SE-171 77, Sweden [2] Department of Numerical Analysis and Computer Science, SciLifeLab, Stockholm University, Stockholm SE-106 91, Sweden., Gambaro G; Division of Nephrology, Department of Internal Medicine and Medical Specialties, Columbus-Gemelli University Hospital, Catholic University, Rome 00168, Italy., Giulianini F; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA., Goddard WA 3rd; Materials and Process Simulation Center, California Institute of Technology, Pasadena, California 91125, USA., Goel A; Department of Cardiovascular Medicine, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK., Gottesman O; The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA., Grove ML; Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas 77225, USA., Gustafsson S; Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala SE-751 85, Sweden., Hai Y; Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502, USA., Hallmans G; Department of Biobank Research, Umeå University, Umeå SE-901 87, Sweden., Heo J; Department of Biomedical Technology, Sangmyung University, Chungnam 330-720, Korea., Hoffmann P; 1] Institute of Human Genetics, Department of Genomics, Life &Brain Center, University of Bonn, Bonn DE-53127, Germany [2] Human Genomics Research Group, Division of Medical Genetics, University Hospital Basel Department of Biomedicine 4031, Basel, Switzerland [3] Institute of Neuroscience and Medicine (INM-1) Genomic Imaging Research Center Juelich, Juelich DE-52425, Germany., Ikram MK; 1] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore [2] Office of Clinical Sciences, Duke-NUS Graduate Medical School, National University of Singapore, Singapore 169857, Singapore [3] Memory Aging &Cognition Centre (MACC), National University Health System, Singapore 117599, Singapore., Jensen RA; 1] Cardiovascular Health Research Unit, University of Washington, Seattle, Washington 98101, USA [2] Department of Medicine, University of Washington, Seattle, Washington 98195, USA., Jørgensen ME; Steno Diabetes Center, Gentofte DK-2820, Denmark., Jørgensen T; 1] Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup DK-2600, Denmark [2] Faculty of Medicine, University of Aalborg, Aalborg DK-9220, Denmark., Karaleftheri M; Echinos Medical Centre, Echinos 67300, Greece., Khor CC; 1] Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119228, Singapore [2] Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 119228, Singapore [3] Division of Human Genetics, Genome Institute of Singapore, Singapore 138672, Singapore., Kirkpatrick A; Materials and Process Simulation Center, California Institute of Technology, Pasadena, California 91125, USA., Kraja AT; Division of Statistical Genomics and Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63108, USA., Kuusisto J; Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio FI-70211, Finland., Lange EM; 1] Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA [2] Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina 27599, USA., Lee IT; 1] Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan [2] School of Medicine, National Yang-Ming University, Taipei 112, Taiwan., Lee WJ; Department of Medical Research, Taichung Veterans General Hospital, Taichung 407, Taiwan., Leong A; 1] Massachusetts General Hospital, General Medicine Division, Boston, Massachusetts 02114, USA [2] Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA., Liao J; 1] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore [2] Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119228, Singapore., Liu C; National Heart, Lung, and Blood Institute (NHLBI) Framingham Heart Study, Framingham, Massachusetts 01702, USA., Liu Y; Department of Epidemiology &Prevention, Division of Public Health Sciences, Wake Forest University, Winston-Salem, North Carolina 27106, USA., Lindgren CM; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK., Linneberg A; 1] Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup DK-2600, Denmark [2] Department of Clinical Experimental Research, Copenhagen University Hospital Glostrup, Glostrup DK-2600, Denmark [3] Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen DK-2200, Denmark., Malerba G; Section of Biology and Genetics, Department of Life and Reproduction Sciences, University of Verona, Verona 37100, Italy., Mamakou V; 1] National and Kapodistrian University of Athens, Faculty of Medicine, Athens 115 27, Greece [2] Dromokaiteio Psychiatric Hospital, Athens 124 61, Greece., Marouli E; Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens 17671, Greece., Maruthur NM; 1] Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland 21205, USA., Matchan A; The Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK., McKean-Cowdin R; Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles 90033, USA., McLeod O; Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm SE-171 77, Sweden., Metcalf GA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA., Mohlke KL; Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA., Muzny DM; Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA., Ntalla I; 1] Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens 17671, Greece [2] University of Leicester, Leicester LE1 7RH, UK., Palmer ND; 1] Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA [2] Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina 27106, USA., Pasko D; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK., Peter A; 1] Department of Internal Medicine, Division of Endocrinology, Metabolism, Pathobiochemistry and Clinical Chemistry and Institute of Diabetes Research and Metabolic Diseases, University of Tübingen, Tübingen DE-72076, Germany [2] German Center for Diabetes Research (DZD), Neuherberg DE-85764, Germany., Rayner NW; 1] The Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK [2] Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, UK [3] The Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LE, UK., Renström F; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Skåne University Hospital, Malmö SE-205 02, Sweden., Rice K; 1] Cardiovascular Health Research Unit, University of Washington, Seattle, Washington 98101, USA [2] Department of Biostatistics, University of Washington, Seattle, Washington 98195, USA., Sala CF; Division of Genetics and Cell Biology, San Raffaele Research Institute, Milano 20132, Italy., Sennblad B; 1] Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm SE-171 77, Sweden [2] Science for Life Laboratory, Karolinska Institutet, Stockholm SE-171 77, Sweden., Serafetinidis I; Department of Gastroenterology, Gennimatas General Hospital, Athens 11527, Greece., Smith JA; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan 48109, USA., Soranzo N; 1] The Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK [2] Department of Hematology, Long Road, Cambridge CB2 0XY, UK., Speliotes EK; Department of Internal Medicine, Division of Gastroenterology and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA., Stahl EA; Division of Psychiatric Genomics, The Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA., Stirrups K; 1] The Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK [2] William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 4NS, UK., Tentolouris N; First Department of Propaedeutic and Internal Medicine, Athens University Medical School, Laiko General Hospital, Athens 11527, Greece., Thanopoulou A; Diabetes Centre, 2nd Department of Internal Medicine, National University of Athens, Hippokration General Hospital, Athens 11527, Greece., Torres M; Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles 90033, USA., Traglia M; Division of Genetics and Cell Biology, San Raffaele Research Institute, Milano 20132, Italy., Tsafantakis E; Anogia Medical Centre, Anogia 740 51, Greece., Javad S; MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0SL, UK., Yanek LR; The GeneSTAR Research Program, Division of General Internal Medicine, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA., Zengini E; 1] Dromokaiteio Psychiatric Hospital, Athens 124 61, Greece [2] University of Sheffield, Sheffield S10 2TN, UK., Becker DM; The GeneSTAR Research Program, Division of General Internal Medicine, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA., Bis JC; 1] Cardiovascular Health Research Unit, University of Washington, Seattle, Washington 98101, USA [2] Department of Medicine, University of Washington, Seattle, Washington 98195, USA., Brown JB; 1] Department of Genome Dynamics, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA [2] Department of Statistics, University of California at Berkeley, Berkeley, California 94720, USA., Cupples LA; 1] National Heart, Lung, and Blood Institute (NHLBI) Framingham Heart Study, Framingham, Massachusetts 01702, USA [2] Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA., Hansen T; 1] The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen DK-2200, Denmark [2] Faculty of Health Science, University of Copenhagen, Copenhagen 1165, Denmark., Ingelsson E; 1] Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala SE-751 85, Sweden [2] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK., Karter AJ; Division of Research, Kaiser Permanente, Northern California Region, Oakland, California 94612, USA., Lorenzo C; Department of Medicine, University of Texas Health Science Center, San Antonio, Texas 77030, USA., Mathias RA; The GeneSTAR Research Program, Division of General Internal Medicine, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA., Norris JM; Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado 80204, USA., Peloso GM; 1] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA [2] Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA., Sheu WH; 1] Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan [2] School of Medicine, National Yang-Ming University, Taipei 112, Taiwan [3] College of Medicine, National Defense Medical Center, Taipei 114, Taiwan., Toniolo D; Division of Genetics and Cell Biology, San Raffaele Research Institute, Milano 20132, Italy., Vaidya D; The GeneSTAR Research Program, Division of General Internal Medicine, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA., Varma R; Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles 90033, USA., Wagenknecht LE; Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina 27106, USA., Boeing H; Department of Epidemiology, German Institute of Human Nutrition Potsdam Rehbrücke, Nuthetal DE-14558, Germany., Bottinger EP; The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA., Dedoussis G; Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens 17671, Greece., Deloukas P; 1] William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 4NS, UK [2] Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK [3] Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah 22254, Saudi Arabia., Ferrannini E; CNR Institute of Clinical Physiology, Pisa 73100, Italy., Franco OH; Department of Epidemiology, Erasmus University Medical Center, Rotterdam 3000 CE, The Netherlands., Franks PW; 1] Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Skåne University Hospital, Malmö SE-205 02, Sweden [2] Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA [3] Department of Public Health &Clinical Medicine, Umeå University, Umeå SE-901 87, Sweden., Gibbs RA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA., Gudnason V; 1] Icelandic Heart Association, Holtasmari 1, Kopavogur IS-201, Iceland [2] University of Iceland, Reykjavik IS-101, Iceland., Hamsten A; Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm SE-171 77, Sweden., Harris TB; Intramural Research Program, National Institute on Aging, Bethesda, Maryland 21224, USA., Hattersley AT; Genetics of Diabetes, University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK., Hayward C; MRC Human Genetics Unit, MRC IGMM, University of Edinburgh, Edinburgh, Scotland EH4 2XU, UK., Hofman A; Department of Epidemiology, Erasmus University Medical Center, Rotterdam 3000 CE, The Netherlands., Jansson JH; 1] Department of Public Health &Clinical Medicine, Umeå University, Umeå SE-901 87, Sweden [2] Research Unit, Skellefteå SE-931 87, Sweden., Langenberg C; MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0SL, UK., Launer LJ; Intramural Research Program, National Institute on Aging, Bethesda, Maryland 21224, USA., Levy D; 1] Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA [2] Framingham Heart Study, Framingham, Massachusetts 01702, USA., Oostra BA; Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam 3000 CE, The Netherlands., O'Donnell CJ; 1] National Heart, Lung, and Blood Institute (NHLBI) Framingham Heart Study, Framingham, Massachusetts 01702, USA [2] Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA [3] Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA., O'Rahilly S; University of Cambridge Metabolic Research Laboratories, MRC Metabolic Diseases Unit and NIHR Cambridge Biomedical Research Centre, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 1TN, UK., Padmanabhan S; Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8TA, UK., Pankow JS; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota 55455, USA., Polasek O; Department of Public Health, Faculty of Medicine, University of Split, Split 21000, Croatia., Province MA; Division of Statistical Genomics and Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63108, USA., Rich SS; Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia 22908, USA., Ridker PM; 1] Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA [2] Division of Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA., Rudan I; Centre for Population Health Sciences, Medical School, University of Edinburgh, Edinburgh, Scotland EH8 9YL, UK., Schulze MB; 1] Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal DE-14558, Germany [2] German Center for Diabetes Research (DZD), Neuherberg DE-85764, Germany., Smith BH; Medical Research Institute, University of Dundee, Dundee DD1 9SY, UK., Uitterlinden AG; 1] Department of Internal Medicine, Erasmus University Medical Center, Rotterdam 3000 CE, The Netherlands [2] Department of Epidemiology, Erasmus University Medical Center, Rotterdam 3000 CE, The Netherlands., Walker M; Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne NE1 7RU, UK., Watkins H; Department of Cardiovascular Medicine, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK., Wong TY; 1] Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore [2] Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119228, Singapore [3] Office of Clinical Sciences, Duke-NUS Graduate Medical School, National University of Singapore, Singapore 169857, Singapore., Zeggini E; The Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK., Laakso M; Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio FI-70211, Finland., Borecki IB; Division of Statistical Genomics and Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63108, USA., Chasman DI; 1] Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA [2] Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA., Pedersen O; The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen DK-2200, Denmark., Psaty BM; 1] Cardiovascular Health Research Unit, University of Washington, Seattle, Washington 98101, USA [2] Department of Medicine, University of Washington, Seattle, Washington 98195, USA [3] Department of Epidemiology, University of Washington, Seattle, Washington 98195, USA [4] Department of Health Services, University of Washington, Seattle, Washington 98195, USA [5] Group Health Research Institute, Group Health Cooperative, Seattle, Washington 98195, USA., Tai ES; 1] Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 119228, Singapore [2] Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore., van Duijn CM; 1] Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam 3000 CE, The Netherlands [2] Center for Medical Systems Biology, Leiden 2300, The Netherlands., Wareham NJ; MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0SL, UK., Waterworth DM; Genetics, PCPS, GlaxoSmithKline, Philadelphia, Pennsylvania 19104, USA., Boerwinkle E; 1] Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas 77225, USA [2] Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA., Kao WH; 1] Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland 21205, USA [2] Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland 21205, USA [3] Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA., Florez JC; 1] Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Diabetes Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA [3] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts 02142, USA [4] Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA., Loos RJ; 1] The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA [2] The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA [3] The Mindich Child Health and Development Institute, The Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA., Wilson JG; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi 38677, USA., Frayling TM; Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK., Siscovick DS; 1] New York Academy of Medicine, New York, New York 10029, USA [2] Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology, University of Washington, Seattle, Washington 98195, USA., Dupuis J; 1] National Heart, Lung, and Blood Institute (NHLBI) Framingham Heart Study, Framingham, Massachusetts 01702, USA [2] Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA., Rotter JI; Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502, USA., Meigs JB; 1] Massachusetts General Hospital, General Medicine Division, Boston, Massachusetts 02114, USA [2] Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA., Scott RA; MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0SL, UK., Goodarzi MO; 1] Department of Medicine and Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA [2] Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2015 Jan 29; Vol. 6, pp. 5897. Date of Electronic Publication: 2015 Jan 29.
DOI: 10.1038/ncomms6897
Abstrakt: Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF=1.4%) with lower FG (β=-0.09±0.01 mmol l(-1), P=3.4 × 10(-12)), T2D risk (OR[95%CI]=0.86[0.76-0.96], P=0.010), early insulin secretion (β=-0.07±0.035 pmolinsulin mmolglucose(-1), P=0.048), but higher 2-h glucose (β=0.16±0.05 mmol l(-1), P=4.3 × 10(-4)). We identify a gene-based association with FG at G6PC2 (pSKAT=6.8 × 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF=20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (β=0.02±0.004 mmol l(-1), P=1.3 × 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
Databáze: MEDLINE