Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes.

Autor: Goodrich JK; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Singer-Berk M; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Son R; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Sveden A; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Wood J; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA., England E; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Cole JB; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Weisburd B; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Watts N; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Caulkins L; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Dornbos P; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Koesterer R; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Zappala Z; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Zhang H; School of Medicine, University of Maryland Baltimore, Baltimore, MD, USA., Maloney KA; School of Medicine, University of Maryland Baltimore, Baltimore, MD, USA., Dahl A; Department of Neurology, UCLA, Los Angeles, CA, USA., Aguilar-Salinas CA; Instituto Nacional de Ciencias Medicas y Nutricion, Mexico City, Mexico., Atzmon G; Department of Medicine, Albert Einstein College of Medicine, New York, NY, USA.; Faculty of Natural Science, University of Haifa, Haifa, Israel.; Department of Genetics, Albert Einstein College of Medicine, New York, NY, USA., Barajas-Olmos F; Instituto Nacional de Medicina Genómica, Mexico City, Mexico., Barzilai N; Department of Medicine, Albert Einstein College of Medicine, New York, NY, USA.; Department of Genetics, Albert Einstein College of Medicine, New York, NY, USA., Blangero J; Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville and Edinburg, TX, USA., Boerwinkle E; Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA., Bonnycastle LL; Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Bottinger E; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Bowden DW; Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.; Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA., Centeno-Cruz F; Instituto Nacional de Medicina Genómica, Mexico City, Mexico., Chambers JC; Department of Epidemiology and Biostatistics, Imperial College London, London, UK.; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore., Chami N; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; The Mindich Child Health and Development Institute, Ichan School of Medicine at Mount Sinai, New York, NY, USA., Chan E; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore., Chan J; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.; Chinese University of Hong Kong-Shanghai Jiao Tong University Joint Research Centre in Diabetes Genomics and Precision Medicine, The Chinese University of Hong Kong, Hong Kong, China.; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China.; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China., Cheng CY; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore.; Duke-NUS Medical School, Singapore, Singapore., Cho YS; Department of Biomedical Science, Hallym University, Chuncheon, South Korea., Contreras-Cubas C; Instituto Nacional de Medicina Genómica, Mexico City, Mexico., Córdova E; Instituto Nacional de Medicina Genómica, Mexico City, Mexico., Correa A; Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA., DeFronzo RA; Department of Medicine, University of Texas Health San Antonio (aka University of Texas Health Science Center at San Antonio), San Antonio, TX, USA., Duggirala R; Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville and Edinburg, TX, USA., Dupuis J; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA., Garay-Sevilla ME; Department of Medical Science, División of Health Science, University of Guanjuato. Campus León. León, Guanjuato, Mexico., García-Ortiz H; Instituto Nacional de Medicina Genómica, Mexico City, Mexico., Gieger C; Research Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany., Glaser B; Endocrinology and Metabolism Service, Hadassah-Hebrew University Medical Center, Jerusalem, Israel., González-Villalpando C; Unidad de Investigacion en Diabetes y Riesgo Cardiovascular, Instituto Nacional de Salud Publica, Cuernavaca, Mexico., Gonzalez ME; Centro de Estudios en Diabetes, Mexico City, Mexico., Grarup N; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Groop L; Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Malmö, Sweden.; Institute for Molecular Genetics Finland, University of Helsinki, Helsinki, Finland., Gross M; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA., Haiman C; Department of Preventive Medicine, Keck School of Medicine of USC, Los Angeles, CA, USA., Han S; Division of Genome Research, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, South Korea., Hanis CL; Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA., Hansen T; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Heard-Costa NL; Boston University and National Heart Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA.; Department of Neurology, Boston University School of Medicine, Boston, MA, USA., Henderson BE; Department of Preventive Medicine, Keck School of Medicine of USC, Los Angeles, CA, USA., Hernandez JMM; Department of Medical Science, División of Health Science, University of Guanjuato. Campus León. León, Guanjuato, Mexico., Hwang MY; Division of Genome Research, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, South Korea., Islas-Andrade S; Instituto Nacional de Medicina Genómica, Mexico City, Mexico., Jørgensen ME; Steno Diabetes Center Copenhagen, Gentofte, Denmark.; National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark.; Greenland Centre for Health Research, University of Greenland, Nuuk, Greenland., Kang HM; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA., Kim BJ; Division of Genome Research, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, South Korea., Kim YJ; Division of Genome Research, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, South Korea., Koistinen HA; Department of Public Health Solutions, Finnish Institute for Health and Welfare, Helsinki, Finland.; University of Helsinki and Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.; Minerva Foundation Institute for Medical Research, Helsinki, Finland., Kooner JS; Department of Cardiology, Ealing Hospital, London North West Healthcare NHS Trust, London, UK.; MRC-PHE Centre for Environment and Health, Imperial College London, London, UK.; Imperial College Healthcare NHS Trust, Imperial College London, London, UK.; National Heart and Lung Institute, Imperial College London, London, UK., Kuusisto J; Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland., Kwak SH; Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea., Laakso M; Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland., Lange L; Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA., Lee JY; Oneomics Soonchunhyang Mirae Medical Center, Bucheon-si Gyeonggi-do, Republic of Korea., Lee J; Division of Genome Research, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, South Korea., Lehman DM; Department of Medicine, University of Texas Health San Antonio (aka University of Texas Health Science Center at San Antonio), San Antonio, TX, USA., Linneberg A; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.; Department of Clinical Experimental Research, Rigshospitalet, Copenhagen, Denmark., Liu J; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore.; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.; Genome Institute of Singapore, Agency for Science Technology and Research, Singapore, Singapore., Loos RJF; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; The Mindich Child Health and Development Institute, Ichan School of Medicine at Mount Sinai, New York, NY, USA., Lyssenko V; Centro de Estudios en Diabetes, Mexico City, Mexico.; Department of Clinical Science, University of Bergen, Bergen, Norway., Ma RCW; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.; Chinese University of Hong Kong-Shanghai Jiao Tong University Joint Research Centre in Diabetes Genomics and Precision Medicine, The Chinese University of Hong Kong, Hong Kong, China.; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China.; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China., Martínez-Hernández A; Instituto Nacional de Medicina Genómica, Mexico City, Mexico., Meigs JB; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA.; Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA, USA., Meitinger T; Institute of Human Genetics, Technical University of Munich, Munich, Germany.; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany., Mendoza-Caamal E; Instituto Nacional de Medicina Genómica, Mexico City, Mexico., Mohlke KL; Department of Genetics, University of North Carolina Chapel Hill, Chapel Hill, NC, USA., Morris AD; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.; Department of Biostatistics, University of Liverpool, Liverpool, UK., Morrison AC; Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA., Ng MCY; Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.; Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA., Nilsson PM; Department of Clinical Sciences, Medicine, Lund University, Malmö, Sweden., O'Donnell CJ; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.; Section of Cardiology, Department of Medicine, VA Boston Healthcare, Boston, MA, USA.; Brigham and Women's Hospital, Boston, MA, USA.; Intramural Administration Management Branch, National Heart Lung and Blood Institute, NIH, Framingham, MA, USA., Orozco L; Instituto Nacional de Medicina Genómica, Mexico City, Mexico., Palmer CNA; Pat Macpherson Centre for Pharmacogenetics and Pharmacogenomics, University of Dundee, Dundee, UK., Park KS; Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, South Korea., Post WS; Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA., Pedersen O; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Preuss M; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Psaty BM; Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, USA.; Kaiser Permanente Washington Research Institute, Seattle, WA, USA., Reiner AP; Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Revilla-Monsalve C; Instituto Nacional de Medicina Genómica, Mexico City, Mexico., Rich SS; Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, USA., Rotter JI; The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation (formerly Los Angeles Biomedical Research Institute) at Harbor-UCLA Medical Center, Torrance, CA, USA., Saleheen D; Division of Translational Medicine and Human Genetics, University of Pennsylvania, Philadelphia, PA, USA.; Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA.; Center for Non-Communicable Diseases, Karachi, Pakistan., Schurmann C; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Digital Health Center, Hasso Plattner Institute, University of Potsdam, Prof.-Dr.-Helmert-Str. 2-3, Potsdam, Germany.; Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, USA., Sim X; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore., Sladek R; Department of Human Genetics, McGill University, Montreal, QC, Canada.; Division of Endocrinology and Metabolism, Department of Medicine, McGill University, Montreal, QC, Canada.; McGill University and Génome Québec Innovation Centre, Montreal, QC, Canada., Small KS; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK., So WY; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.; Chinese University of Hong Kong-Shanghai Jiao Tong University Joint Research Centre in Diabetes Genomics and Precision Medicine, The Chinese University of Hong Kong, Hong Kong, China.; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China., Spector TD; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK., Strauch K; Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany.; Institute for Medical Informatics Biometry and Epidemiology, Ludwig-Maximilians University, Munich, Germany., Strom TM; Institute of Human Genetics, Technical University of Munich, Munich, Germany.; Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany., Tai ES; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore.; Duke-NUS Medical School, Singapore, Singapore.; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore., Tam CHT; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.; Chinese University of Hong Kong-Shanghai Jiao Tong University Joint Research Centre in Diabetes Genomics and Precision Medicine, The Chinese University of Hong Kong, Hong Kong, China.; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China., Teo YY; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.; Life Sciences Institute, National University of Singapore, Singapore, Singapore.; Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore., Thameem F; Department of Biochemistry, Faculty of Medicine, Health Science Center, Kuwait University, Safat, Kuwait., Tomlinson B; Faculty of Medicine, Macau University of Science & Technology, Macau, China., Tracy RP; Department of Pathology and Laboratory Medicine, The Robert Larner M.D. College of Medicine, University of Vermont, Burlington, VT, USA.; Department of Biochemistry, The Robert Larner M.D. College of Medicine, University of Vermont, Burlington, VT, USA., Tuomi T; Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Malmö, Sweden.; Institute for Molecular Genetics Finland, University of Helsinki, Helsinki, Finland.; Folkhälsan Research Centre, Helsinki, Finland.; Department of Endocrinology, Abdominal Centre, Helsinki University Hospital, Helsinki, Finland.; Research Programs Unit, Clinical and Molecular Medicine, University of Helsinki, Helsinki, Finland., Tuomilehto J; Public Health Promotion Unit, Finnish Institute for Health and Welfare, Helsinki, Finland.; Department of Public Health, University of Helsinki, Helsinki, Finland.; Saudi Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia.; Department of International Health, National School of Public Health, Instituto de Salud Carlos III, Madrid, Spain., Tusié-Luna T; Unidad de Biología Molecular y Medicina Genómica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.; Departamento de Medicina Genómica y Toxiología Ambiental, Instituto de Investigaciones Biomédicas, UNAM, Mexico City, Mexico., van Dam RM; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore.; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA., Vasan RS; Boston University and National Heart Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA.; Preventive Medicine & Epidemiology, and Cardiovascular Medicine, Medicine, Boston University School of Medicine, and Epidemiology, Boston University School of Public health, Boston, MA, USA., Wilson JG; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA., Witte DR; Department of Public Health, Aarhus University, Aarhus, Denmark.; Danish Diabetes Academy, Odense, Denmark., Wong TY; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore.; Duke-NUS Medical School, Singapore, Singapore., Burtt NP; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Zaitlen N; Department of Neurology, UCLA, Los Angeles, CA, USA., McCarthy MI; Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.; Genentech, South San Francisco, CA, USA., Boehnke M; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA., Pollin TI; School of Medicine, University of Maryland Baltimore, Baltimore, MD, USA., Flannick J; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Division of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA, USA., Mercader JM; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA., O'Donnell-Luria A; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Division of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts, USA.; Department of Pediatrics, Harvard Medical School, Boston, MA, USA., Baxter S; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Florez JC; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA., MacArthur DG; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Centre for Population Genomics, Garvan Institute of Medical Research, UNSW Sydney, Sydney, NSW, Australia.; Centre for Population Genomics, Murdoch Children's Research Institute, Melbourne, VIC, Australia., Udler MS; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. mudler@mgh.harvard.edu.; Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. mudler@mgh.harvard.edu.; Department of Medicine, Harvard Medical School, Boston, MA, USA. mudler@mgh.harvard.edu.

Publikováno v: Nature communications [Nat Commun] 2021 Jun 09; Vol. 12 (1), pp. 3505. Date of Electronic Publication: 2021 Jun 09.