Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes
Por:
Goodrich, Julia K., Singer-Berk, Moriel, Son, Rachel, Sveden, Abigail, Wood, Jordan, England, Eleina, Cole, Joanne B., Weisburd, Ben, Watts, Nick, Caulkins, Lizz, Dornbos, Peter, Koesterer, Ryan, Zappala, Zachary, Zhang, Haichen, Maloney, Kristin A., Dahl, Andy, Aguilar-Salinas, Carlos A., Atzmon, Gil, Barajas-Olmos, Francisco, Barzilai, Nir, Blangero, John, Boerwinkle, Eric, Bonnycastle, Lori L., Bottinger, Erwin, Bowden, Donald W., Centeno-Cruz, Federico, Chambers, John C., Chami, Nathalie, Chan, Edmund, Chan, Juliana, Cheng, Ching-Yu, Cho, Yoon Shin, Contreras-Cubas, Cecilia, Cordova, Emilio, Correa, Adolfo, DeFronzo, Ralph A., Duggirala, Ravindranath, Dupuis, Josee, Garay-Sevilla M.E., Garcia-Ortiz, Humberto, Gieger, Christian, Glaser, Benjamin, Gonzalez-Villalpando, Clicerio, Gonzalez M.E., Grarup, Niels, Groop, Leif, Gross, Myron, Haiman, Christopher, Han, Sohee, Hanis, Craig L., Hansen, Torben, Heard-Costa, Nancy L., Henderson, Brian E., Hernandez J.M.M., Hwang, Mi Yeong, Islas-Andrade, Sergio, Jørgensen M.E., Kang, Hyun Min, Kim B.-J., Kim, Young Jin, Koistinen, Heikki A., Kooner, Jaspal Singh, Kuusisto, Johanna, Kwak S.-H., Laakso, Markku, Lange, Leslie, Lee J.-Y., Lee, Juyoung, Lehman, Donna M., Linneberg, Allan, Liu, Jianjun, Loos R.J.F., Lyssenko, Valeriya, Ma R.C.W., Martinez-Hernandez, Angelica, Meigs, James B., Meitinger, Thomas, Mendoza-Caamal, Elvia, Mohlke, Karen L., Morris, Andrew D., Morrison, Alanna C., Ng M.C.Y., Nilsson, Peter M., O'Donnell, Christopher J., Orozco, Lorena, Palmer C.N.A., Park, Kyong Soo, Post, Wendy S., Pedersen, Oluf, Preuss, Michael, Psaty, Bruce M., Reiner, Alexander P., Revilla-Monsalve, Cristina, Rich, Stephen S., Rotter, Jerome I., Saleheen, Danish, Schurmann, Claudia, Sim, Xueling, Sladek, Rob, Small, Kerrin S., So, Wing Yee, Spector, Timothy D., Strauch, Konstantin, Strom, Tim M., Tai, E. Shyong, Tam C.H.T., Teo, Yik Ying, Thameem, Farook, Tomlinson, Brian, Tracy, Russell P., Tuomi, Tiinamaija, Tuomilehto, Jaakko, Tusie-Luna, Teresa, van Dam, Rob M., Vasan, Ramachandran S., Wilson, James G., Witte, Daniel R., Wong T.-Y., Burtt, Noel P., Zaitlen, Noah, McCarthy, Mark I., Boehnke, Michael, Pollin, Toni I., Flannick, Jason, Mercader, Josep M., O'Donnell-Luria, Anne, Baxter, Samantha, Florez, Jose C., MacArthur, Daniel G., Udler, Miriam S., AMP-T2D-GENES Consortia
Publicada:
9 jun 2021
Resumen:
Hundreds of thousands of genetic variants have been reported to cause
severe monogenic diseases, but the probability that a variant carrier
develops the disease (termed penetrance) is unknown for virtually all of
them. Additionally, the clinical utility of common polygenetic variation
remains uncertain. Using exome sequencing from 77,184 adult individuals
(38,618 multi-ancestral individuals from a type 2 diabetes case-control
study and 38,566 participants from the UK Biobank, for whom genotype
array data were also available), we apply clinical standard-of-care gene
variant curation for eight monogenic metabolic conditions. Rare variants
causing monogenic diabetes and dyslipidemias display effect sizes
significantly larger than the top 1% of the corresponding polygenic
scores. Nevertheless, penetrance estimates for monogenic variant
carriers average 60% or lower for most conditions. We assess
epidemiologic and genetic factors contributing to risk prediction in
monogenic variant carriers, demonstrating that inclusion of polygenic
variation significantly improves biomarker estimation for two monogenic
dyslipidemias. Penetrance of variants in monogenic disease and clinical
utility of common polygenic variation has not been well explored on a
large-scale. Here, the authors use exome sequencing data from 77,184
individuals to generate penetrance estimates and assess the utility of
polygenic variation in risk prediction of monogenic variants.
Filiaciones:
Goodrich, Julia K.:
Program in Medical and Population Genetics, Broad Institute of mit and Harvard, Cambridge, MA, United States
Singer-Berk, Moriel:
Program in Medical and Population Genetics, Broad Institute of mit and Harvard, Cambridge, MA, United States
Son, Rachel:
Program in Medical and Population Genetics, Broad Institute of mit and Harvard, Cambridge, MA, United States
Sveden, Abigail:
Program in Medical and Population Genetics, Broad Institute of mit and Harvard, Cambridge, MA, United States
Wood, Jordan:
Program in Medical and Population Genetics, Broad Institute of mit and Harvard, Cambridge, MA, United States
England, Eleina:
Program in Medical and Population Genetics, Broad Institute of mit and Harvard, Cambridge, MA, United States
Cole, Joanne B.:
Program in Medical and Population Genetics, Broad Institute of mit and Harvard, Cambridge, MA, United States
Weisburd, Ben:
Program in Medical and Population Genetics, Broad Institute of mit and Harvard, Cambridge, MA, United States
Watts, Nick:
Program in Medical and Population Genetics, Broad Institute of mit and Harvard, Cambridge, MA, United States
Caulkins, Lizz:
Program in Medical and Population Genetics, Broad Institute of mit and Harvard, Cambridge, MA, United States
Dornbos, Peter:
Program in Medical and Population Genetics, Broad Institute of mit and Harvard, Cambridge, MA, United States
Koesterer, Ryan:
Program in Medical and Population Genetics, Broad Institute of mit and Harvard, Cambridge, MA, United States
Zappala, Zachary:
Program in Medical and Population Genetics, Broad Institute of mit and Harvard, Cambridge, MA, United States
Zhang, Haichen:
School of Medicine, University of Maryland Baltimore, Baltimore, MD, United States
Maloney, Kristin A.:
School of Medicine, University of Maryland Baltimore, Baltimore, MD, United States
Dahl, Andy:
Department of Neurology, UCLA, Los Angeles, CA, United States
Aguilar-Salinas, Carlos A.:
Instituto Nacional de Ciencias Médicas y Nutricion, Mexico City, Mexico
Atzmon, Gil:
Department of Medicine, Albert Einstein College of Medicine, New York, NY, United States
Faculty of Natural Science, University of Haifa, Haifa, Israel
Department of Genetics, Albert Einstein College of Medicine, New York, NY, United States
Barajas-Olmos, Francisco:
Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Barzilai, Nir:
Department of Medicine, Albert Einstein College of Medicine, New York, NY, United States
Department of Genetics, Albert Einstein College of Medicine, New York, NY, United States
Blangero, John:
Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville and Edinburg, TX, United States
Boerwinkle, Eric:
Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, United States
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, United States
Bonnycastle, Lori L.:
Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States
Bottinger, Erwin:
The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
Bowden, Donald W.:
Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, United States
Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, United States
Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, United States
Centeno-Cruz, Federico:
Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Chambers, John C.:
Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
Chami, Nathalie:
The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
The Mindich Child Health and Development Institute, Ichan School of Medicine at Mount Sinai, New York, NY, United States
Chan, Edmund:
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore
Chan, Juliana:
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
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
Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong
Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong
Cheng, Ching-Yu:
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, Yoon Shin:
Department of Biomedical Science, Hallym University, Chuncheon, South Korea
Contreras-Cubas, Cecilia:
Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Cordova, Emilio:
Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Correa, Adolfo:
Department of Medicine, University of Mississippi Medical Center, Jackson, MS, United States
DeFronzo, Ralph A.:
Department of Medicine, University of Texas Health San Antonio (aka University of Texas Health Science Center at San Antonio), San Antonio, TX, United States
Duggirala, Ravindranath:
Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville and Edinburg, TX, United States
Dupuis, Josee:
Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States
Garay-Sevilla M.E.:
Department of Medical Science, División of Health Science, University of Guanjuato. Campus León. León, Guanjuato, Mexico
Garcia-Ortiz, Humberto:
Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Gieger, Christian:
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, Benjamin:
Endocrinology and Metabolism Service, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Gonzalez-Villalpando, Clicerio:
Unidad de Investigacion en Diabetes y Riesgo Cardiovascular, Instituto Nacional de Salud Publica, Cuernavaca, Mexico
Gonzalez M.E.:
Centro de Estudios en Diabetes, Mexico City, Mexico
Grarup, Niels:
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Groop, Leif:
Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Malmö, Sweden
Institute for Molecular Genetics Finland, University of Helsinki, Helsinki, Finland
Gross, Myron:
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, United States
Haiman, Christopher:
Department of Preventive Medicine, Keck School of Medicine of USC, Los Angeles, CA, United States
Han, Sohee:
Division of Genome Research, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, South Korea
Hanis, Craig L.:
Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, United States
Hansen, Torben:
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Heard-Costa, Nancy L.:
Boston University and National Heart Lung and Blood Institute’s Framingham Heart Study, Framingham, MA, United States
Department of Neurology, Boston University School of Medicine, Boston, MA, United States
Henderson, Brian E.:
Department of Preventive Medicine, Keck School of Medicine of USC, Los Angeles, CA, United States
Hernandez J.M.M.:
Department of Medical Science, División of Health Science, University of Guanjuato. Campus León. León, Guanjuato, Mexico
Hwang, Mi Yeong:
Division of Genome Research, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, South Korea
Islas-Andrade, Sergio:
Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Jørgensen M.E.:
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, Hyun Min:
Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, United States
Kim B.-J.:
Division of Genome Research, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, South Korea
Kim, Young Jin:
Division of Genome Research, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, South Korea
Koistinen, Heikki A.:
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, Jaspal Singh:
Department of Cardiology, Ealing Hospital, London North West Healthcare NHS Trust, London, United Kingdom
MRC-PHE Centre for Environment and Health, Imperial College London, London, United Kingdom
Imperial College Healthcare NHS Trust, Imperial College London, London, United Kingdom
National Heart and Lung Institute, Imperial College London, London, United Kingdom
Kuusisto, Johanna:
Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
Kwak S.-H.:
Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
Laakso, Markku:
Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
Lange, Leslie:
Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, United States
Lee J.-Y.:
Oneomics Soonchunhyang Mirae Medical Center, Bucheon-si Gyeonggi-do, South Korea
Lee, Juyoung:
Oneomics Soonchunhyang Mirae Medical Center, Bucheon-si Gyeonggi-do, South Korea
Lehman, Donna M.:
Department of Medicine, University of Texas Health San Antonio (aka University of Texas Health Science Center at San Antonio), San Antonio, TX, United States
Linneberg, Allan:
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, Jianjun:
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 R.J.F.:
The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
The Mindich Child Health and Development Institute, Ichan School of Medicine at Mount Sinai, New York, NY, United States
Lyssenko, Valeriya:
Centro de Estudios en Diabetes, Mexico City, Mexico
Department of Clinical Science, University of Bergen, Bergen, Norway
Ma R.C.W.:
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
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
Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong
Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong
Martinez-Hernandez, Angelica:
Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Meigs, James B.:
Program in Medical and Population Genetics, Broad Institute of mit and Harvard, Cambridge, MA, United States
Department of Medicine, Harvard Medical School, Boston, MA, United States
Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA, United States
Meitinger, Thomas:
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, Elvia:
Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Mohlke, Karen L.:
Department of Genetics, University of North Carolina Chapel Hill, Chapel Hill, NC, United States
Morris, Andrew D.:
Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
Department of Biostatistics, University of Liverpool, Liverpool, United Kingdom
Morrison, Alanna C.:
Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, United States
Ng M.C.Y.:
Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, United States
Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, United States
Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, United States
Nilsson, Peter M.:
Department of Clinical Sciences, Medicine, Lund University, Malmö, Sweden
O'Donnell, Christopher J.:
Department of Pediatrics, Harvard Medical School, Boston, MA, United States
Section of Cardiology, Department of Medicine, VA Boston Healthcare, Boston, MA, United States
Brigham and Women’s Hospital, Boston, MA, United States
Intramural Administration Management Branch, National Heart Lung and Blood Institute, NIH, Framingham, MA, United States
Orozco, Lorena:
Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Palmer C.N.A.:
Pat Macpherson Centre for Pharmacogenetics and Pharmacogenomics, University of Dundee, Dundee, United Kingdom
Park, Kyong Soo:
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, Wendy S.:
Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, United States
Pedersen, Oluf:
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Preuss, Michael:
The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
Psaty, Bruce M.:
Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, United States
Kaiser Permanente Washington Research Institute, Seattle, WA, United States
Reiner, Alexander P.:
Fred Hutchinson Cancer Research Center, Seattle, WA, United States
Revilla-Monsalve, Cristina:
Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Rich, Stephen S.:
Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, United States
Rotter, Jerome I.:
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, United States
Saleheen, Danish:
Division of Translational Medicine and Human Genetics, University of Pennsylvania, Philadelphia, PA, United States
Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, United States
Center for Non-Communicable Diseases, Karachi, Pakistan
Schurmann, Claudia:
The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
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, United States
Sim, Xueling:
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore
Sladek, Rob:
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, Kerrin S.:
Department of Twin Research and Genetic Epidemiology, King’s College London, London, United Kingdom
So, Wing Yee:
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
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
Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong
Spector, Timothy D.:
Department of Twin Research and Genetic Epidemiology, King’s College London, London, United Kingdom
Strauch, Konstantin:
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, Tim M.:
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, E. Shyong:
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 C.H.T.:
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
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
Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong
Teo, Yik Ying:
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, Farook:
Department of Biochemistry, Faculty of Medicine, Health Science Center, Kuwait University, Safat, Kuwait
Tomlinson, Brian:
Faculty of Medicine, Macau University of Science & Technology, Macau, China
Tracy, Russell P.:
Department of Pathology and Laboratory Medicine, The Robert Larner M.D. College of Medicine, University of Vermont, Burlington, VT, United States
Department of Biochemistry, The Robert Larner M.D. College of Medicine, University of Vermont, Burlington, VT, United States
Tuomi, Tiinamaija:
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, Jaakko:
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
Tusie-Luna, Teresa:
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, Rob M.:
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, United States
Vasan, Ramachandran S.:
Boston University and National Heart Lung and Blood Institute’s Framingham Heart Study, Framingham, MA, United States
Preventive Medicine & Epidemiology, and Cardiovascular Medicine, Medicine, Boston University School of Medicine, and Epidemiology, Boston University School of Public health, Boston, MA, United States
Wilson, James G.:
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, United States
Witte, Daniel R.:
Department of Public Health, Aarhus University, Aarhus, Denmark
Danish Diabetes Academy, Odense, Denmark
Wong T.-Y.:
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, Noel P.:
Program in Medical and Population Genetics, Broad Institute of mit and Harvard, Cambridge, MA, United States
Zaitlen, Noah:
Department of Neurology, UCLA, Los Angeles, CA, United States
McCarthy, Mark I.:
Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
Genentech, South San Francisco, CA, United States
Boehnke, Michael:
Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, United States
Pollin, Toni I.:
School of Medicine, University of Maryland Baltimore, Baltimore, MD, United States
Flannick, Jason:
Program in Medical and Population Genetics, Broad Institute of mit and Harvard, Cambridge, MA, United States
Department of Pediatrics, Harvard Medical School, Boston, MA, United States
Division of Genetics and Genomics, Boston Children’s Hospital, Boston, Massachusetts, United States
Mercader, Josep M.:
Program in Medical and Population Genetics, Broad Institute of mit and Harvard, Cambridge, MA, United States
Department of Medicine, Harvard Medical School, Boston, MA, United States
Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, United States
O'Donnell-Luria, Anne:
Program in Medical and Population Genetics, Broad Institute of mit and Harvard, Cambridge, MA, United States
Department of Pediatrics, Harvard Medical School, Boston, MA, United States
Division of Genetics and Genomics, Boston Children’s Hospital, Boston, Massachusetts, United States
Baxter, Samantha:
Program in Medical and Population Genetics, Broad Institute of mit and Harvard, Cambridge, MA, United States
Florez, Jose C.:
Program in Medical and Population Genetics, Broad Institute of mit and Harvard, Cambridge, MA, United States
Department of Medicine, Harvard Medical School, Boston, MA, United States
Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, United States
MacArthur, Daniel G.:
Program in Medical and Population Genetics, Broad Institute of mit and Harvard, Cambridge, MA, United States
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, Miriam S.:
Program in Medical and Population Genetics, Broad Institute of mit and Harvard, Cambridge, MA, United States
Department of Medicine, Harvard Medical School, Boston, MA, United States
Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, United States
gold, Green Published, Green Submitted, All Open Access, Gold, Green
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