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
ISSN: 20411723





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