New Results
Tissue-Specific Alteration of Metabolic Pathways Influences Glycemic Regulation
View ORCID ProfileNatasha H. J. Ng, Sara M. Willems, Juan Fernandez, Rebecca S. Fine, Eleanor Wheeler, Jennifer Wessel, Hidetoshi Kitajima, Gaelle Marenne, Jana K. Rundle, Xueling Sim, Hanieh Yeghootkar, Nicola L. Beer, Anne Raimondo, Andrei I. Tarasov, Soren K. Thomsen, Martijn van de Bunt, Shuai Wang, Sai Chen, Yuning Chen, Yii-Der Ida Chen, Hugoline G. de Haan, Niels Grarup, Ruifang Li-Gao, Tibor V. Varga, Jennifer L Asimit, Shuang Feng, Rona J. Strawbridge, Erica L. Kleinbrink, Tarunveer S. Ahluwalia, Ping An, Emil V. Appel, Dan E Arking, Juha Auvinen, Lawrence F. Bielak, Nathan A. Bihlmeyer, Jette Bork-Jensen, Jennifer A. Brody, Archie Campbell, Audrey Y Chu, Gail Davies, Ayse Demirkan, James S. Floyd, Franco Giulianini, Xiuqing Guo, Stefan Gustafsson, Benoit Hastoy, Anne U. Jackson, Johanna Jakobsdottir, Marjo-Riitta Jarvelin, Richard A. Jensen, Stavroula Kanoni, Sirkka Keinanen-Kiukaanniemi, Jin Li, Man Li, Kurt Lohman, Yingchang Lu, Jian’an Luan, Alisa K. Manning, Jonathan Marten, Carola Marzi, Karina Meidtner, Dennis O. Mook-Kanamori, Taulant Muka, Giorgio Pistis, Bram Prins, Kenneth M. Rice, Neil Robertson, Serena Sanna, Yuan Shi, Albert Vernon Smith, Jennifer A. Smith, Lorraine Southam, Heather M. Stringham, Salman M. Tajuddin, Vinicius Tragante, Sander W. van der Laan, Helen R. Warren, Jie Yao, Andrianos M. Yiorkas, Weihua Zhang, Wei Zhao, Emma Ahlqvist, Mariaelisa Graff, Heather M. Highland, Anne E Justice, Ken Sin Lo, Eirini Marouli, Carolina Medina-Gomez, Saima Afaq, Wesam A Alhejily, Najaf Amin, Folkert W. Asselbergs, Lori L. Bonnycastle, Michiel L. Bots, Ivan Brandslund, Ji Chen, Cramer Christensen, John Danesh, Renée de Mutsert, Abbas Dehghan, Tapani Ebeling, Paul Elliott, EPIC-InterAct Consortium, Aliki-Eleni Farmaki, Jessica D. Faul, Paul W. Franks, Steve Franks, Andreas Fritsche, Anette P. Gjesing, Mark O. Goodarzi, Vilmundur Gudnason, Göran Hallmans, Tamara B. Harris, Karl-Heinz Herzig, Marie-France Hivert, Jan-Håkan Jansson, Min A Jhun, Torben Jørgensen, Marit E. Jørgensen, Pekka Jousilahti, Eero Kajantie, Maria Karaleftheri, Sharon L.R. Kardia, Leena Kinnunen, Heikki A. Koistinen, Pirjo Komulainen, Peter Kovacs, Johanna Kuusisto, Markku Laakso, Leslie A. Lange, Lenore J. Launer, Jung-Jin Lee, Aaron Leong, Jaana Lindström, Jocelyn E. Manning Fox, Satu Männistö, Nisa M Maruthur, Leena Moilanen, Antonella Mulas, Mike A. Nalls, Matthew Neville, James S. Pankow, Alison Pattie, Eva R.B. Petersen, Hannu Puolijoki, Asif Rasheed, Paul Redmond, Frida Renström, Michael Roden, Danish Saleheen, Juha Saltevo, Kai Savonen, Sylvain Sebert, Tea Skaaby, Kerrin S Small, Alena Stančáková, Jakob Stokholm, Konstantin Strauch, E-Shyong Tai, Kent D. Taylor, Betina H. Thuesen, Anke Tönjes, Emmanouil Tsafantakis, Tiinamaija Tuomi, Jaakko Tuomilehto, Understanding Society Scientific Group, Matti Uusitupa, Marja Vääräsmäki, Ilonca Vaartjes, Magdalena Zoledziewska, Goncalo Abecasis, Beverley Balkau, Hans Bisgaard, Alexandra I. Blakemore, Matthias Blüher, Heiner Boeing, Eric Boerwinkle, Klaus Bønnelykke, Erwin P. Bottinger, Mark J. Caulfield, John C Chambers, Daniel I Chasman, Ching-Yu Cheng, Anne Clark, Francis S. Collins, Josef Coresh, Francesco Cucca, Gert J. de Borst, Ian J. Deary, George Dedoussis, Panos Deloukas, Hester M. den Ruijter, Josée Dupuis, Michele K. Evans, Ele Ferrannini, Oscar H Franco, Harald Grallert, Leif Groop, Torben Hansen, Andrew T. Hattersley, Caroline Hayward, Joel N. Hirschhorn, Arfan Ikram, Erik Ingelsson, Fredrik Karpe, Kay-Tee Kaw, Wieland Kiess, Jaspal S Kooner, Antje Körner, Timo Lakka, Claudia Langenberg, Lars Lind, Cecilia M Lindgren, Allan Linneberg, Leonard Lipovich, Ching-Ti Liu, Jun Liu, Yongmei Liu, Ruth J.F. Loos, Patrick E. MacDonald, Karen L. Mohlke, Andrew D Morris, Patricia B. Munroe, Alison Murray, Sandosh Padmanabhan, Colin N A Palmer, Gerard Pasterkamp, Oluf Pedersen, Patricia A. Peyser, Ozren Polasek, David Porteous, Michael A. Province, Bruce M Psaty, Rainer Rauramaa, Paul M Ridker, Olov Rolandsson, Patrik Rorsman, Frits R. Rosendaal, Igor Rudan, Veikko Salomaa, Matthias B. Schulze, Robert Sladek, Blair H Smith, Timothy D Spector, John M. Starr, Michael Stumvoll, Cornelia M van Duijn, Mark Walker, Nick J. Wareham, David R. Weir, James G. Wilson, Tien Yin Wong, Eleftheria Zeggini, Alan B. Zonderman, Jerome I. Rotter, Andrew P. Morris, Michael Boehnke, Jose Florez, Mark I McCarthy, James B Meigs, Anubha Mahajan, Robert A. Scott, Anna L Gloyn, View ORCID ProfileInês Barroso
doi: https://doi.org/10.1101/790618
Natasha H. J. Ng
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LEStem Cells and Diabetes Laboratory, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore
Sara M. Willems
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
Juan Fernandez
Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK, OX3 7BN
Rebecca S. Fine
Department of Genetics, Harvard Medical School, Boston, MA, 02115Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children’s Hospital, Boston, MA 02115Broad Institute of MIT and Harvard, Cambridge, MA, 02142
Eleanor Wheeler
Department of Human Genetics, Wellcome Sanger Institute, Genome Campus, Hinxton, Cambridge, CB10 1SA, UKMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
Jennifer Wessel
Departments of Epidemiology & Medicine, Schools of Public Health & Medicine, Indiana University, Indiaiapolis, IN 46202Diabetes Translational Research Center, Indiana University School of Medicine, Indianapolis, IN 46202
Hidetoshi Kitajima
Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK, OX3 7BN
Gaelle Marenne
Department of Human Genetics, Wellcome Sanger Institute, Genome Campus, Hinxton, Cambridge, CB10 1SA, UK
Jana K. Rundle
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LE
Xueling Sim
Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore 117549, SingaporeDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA
Hanieh Yeghootkar
Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK
Nicola L. Beer
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LE
Anne Raimondo
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LE
Andrei I. Tarasov
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LE
Soren K. Thomsen
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LEVertex Pharmaceuticals Europe Ltd, Milton Park, Abingdon, OX14 4RW, UK
Martijn van de Bunt
Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK, OX3 7BNOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LE
Shuai Wang
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
Sai Chen
Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA
Yuning Chen
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
Yii-Der Ida Chen
Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, LABiomed at Harbor-UCLA Medical Center, Torrance, CA, USA
Hugoline G. de Haan
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, 2333 ZA, the Netherlands
Niels Grarup
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
Ruifang Li-Gao
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, 2333 ZA, the Netherlands
Tibor V. Varga
Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, SE-205 02, Sweden
Jennifer L Asimit
Department of Human Genetics, Wellcome Sanger Institute, Genome Campus, Hinxton, Cambridge, CB10 1SA, UKMRC Biostatistics Unit, Cambridge Biomedical Campus, Cambridge Institute of Public Health, Forvie Site, Robinson Way, Cambridge CB2 0SR, UK
Shuang Feng
Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
Rona J. Strawbridge
UKRI Innovation Fellow at HDR UK,Mental Health and Wellbeing, Institute of Health and Wellbeing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Room 113, 1 Lilybank Gardens, Glasgow, G12 8RZCardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm,171 76, Sweden
Erica L. Kleinbrink
Center for Molecular Medicine and Genetics, Wayne State University, 540 E. Canfield St., 3208 Scott Hall, Detroit, Michigan 48201-1928, U.S.A.
Tarunveer S. Ahluwalia
COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital 2820, University of Copenhagen, Copenhagen, DenmarkSteno Diabetes Center Copenhagen, 2820 Gentofte, Denmark
Ping An
Department of Genetics, Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri 63108, USA
Emil V. Appel
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
Dan E Arking
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Juha Auvinen
Center for Life Course Health Research, University of Oulu, PO Box 8000, 90014 Oulu, FinlandUnit of Primary Care, Oulu University Hospital, Oulu, Finland
Lawrence F. Bielak
Department of Epidemiology, School of Public Health, University of Michigan, 1415 Washington Hgts, Ann Arbor, MI, 48109, USA
Nathan A. Bihlmeyer
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Jette Bork-Jensen
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
Jennifer A. Brody
Cardiovascular Health Research Unit, University of Washington, 1730 Minor Ave. Suite 1360, Seattle, WA 98101, USADepartment of Medicine, University of Washington, Seattle, WA, USA
Archie Campbell
Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK
Audrey Y Chu
Division of Preventive Medicine, Brigham and Women’s Hospital, Boston MA, 02215, USA
Gail Davies
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZDepartment of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ
Ayse Demirkan
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 GE, The Netherlands
James S. Floyd
Cardiovascular Health Research Unit, University of Washington, 1730 Minor Ave. Suite 1360, Seattle, WA 98101, USADepartment of Medicine, University of Washington, Seattle, WA, USA
Franco Giulianini
Division of Preventive Medicine, Brigham and Women’s Hospital, Boston MA, 02215, USA
Xiuqing Guo
Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, LABiomed at Harbor-UCLA Medical Center, Torrance, CA, USA
Stefan Gustafsson
Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, 75237, Sweden
Benoit Hastoy
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LE
Anne U. Jackson
Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA
Johanna Jakobsdottir
Icelandic Heart Association, Hotlasmari 1, 201 Kopavogur, Iceland
Marjo-Riitta Jarvelin
Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of Public Health, Imperial College London, London W2 1PG, United KingdomCenter for Life Course Health Research, University of Oulu, PO Box 8000, 90014 Oulu, FinlandBiocenter Oulu, University of Oulu, Oulu, Finland
Richard A. Jensen
Cardiovascular Health Research Unit, University of Washington, 1730 Minor Ave. Suite 1360, Seattle, WA 98101, USADepartment of Medicine, University of Washington, Seattle, WA, USA
Stavroula Kanoni
William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK
Sirkka Keinanen-Kiukaanniemi
Faculty of Medicine, Center for Life Course Health Research, University of Oulu, Oulu, FinlandMRC and Unit of Primary Care, Oulu University Hospital, Oulu, Finland
Jin Li
Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
Man Li
Division of Nephrology, Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UtahDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Kurt Lohman
Department of Biostatistical Sciences, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157
Yingchang Lu
The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY, 10069, USADepartment of Medicine, Division of Epidemiology, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine Nashville, TN 37203 USA
Jian’an Luan
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
Alisa K. Manning
Center for Human Genetics Research, Massachusetts General Hospital, Boston, MA, 02114, USADepartment of Medicine, Harvard Medical School, Boston, MA, USA
Jonathan Marten
Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK
Carola Marzi
Institute of Epidemiology II, Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, GermanGerman Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany
Karina Meidtner
Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, GermanyGerman Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany
Dennis O. Mook-Kanamori
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, 2333 ZA, the NetherlandsDepartment of Public Health and Primary Care, Leiden University Medical Center, Leiden, 2333 ZA, the Netherlands
Taulant Muka
Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, SwitzerlandDepartment of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 GE, The Netherlands
Giorgio Pistis
Italian National Research Council, Institute of Genetics and Biomedic Research, Cittadella Universitaria, Monserrato (CA) 09042, ItalyCenter for Statistical Genetics, University of Michigan, 1415 Washington Heights, 48109 Ann Arbor, MI, USA
Bram Prins
Department of Human Genetics, Wellcome Sanger Institute, Genome Campus, Hinxton, Cambridge, CB10 1SA, UK
Kenneth M. Rice
Cardiovascular Health Research Unit, University of Washington, 1730 Minor Ave. Suite 1360, Seattle, WA 98101, USADepartment of Biostatistics, University of Washington, Seattle, WA, USA
Neil Robertson
Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK, OX3 7BN
Serena Sanna
Italian National Research Council, Institute of Genetics and Biomedic Research, Cittadella Universitaria, Monserrato (CA) 09042, ItalyUniversity of Groningen, University Medical Center Groningen, Department of Genetics, 9700 RB Groningen, the Netherlands
Yuan Shi
Singapore Eye Research Institute, Singapore National Eye Centre, The Academia, 20 College Road, Singapore 169856
Albert Vernon Smith
Icelandic Heart Association, Hotlasmari 1, 201 Kopavogur, IcelandFaculty of Medicine, University of Iceland, 101 Reykjavik, Iceland
Jennifer A. Smith
Department of Epidemiology, School of Public Health, University of Michigan, 1415 Washington Hgts, Ann Arbor, MI, 48109, USASurvey Research Center, Institute for Social Research, University of Michigan, 426 Thompson St, Ann Arbor, MI 48104
Lorraine Southam
Department of Human Genetics, Wellcome Sanger Institute, Genome Campus, Hinxton, Cambridge, CB10 1SA, UKWellcome Centre for Human Genetics, University of Oxford, Oxford, UK, OX3 7BNInstitute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
Heather M. Stringham
Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA
Salman M. Tajuddin
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
Vinicius Tragante
Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, 3584CX Utrecht, The Netherlands
Sander W. van der Laan
Experimental Cardiology Laboratory, Division Heart and Lungs, University Medical Center Utrecht, 3584 CX Utrecht, Utrecht, the NetherlandsLaboratory of Clinical Chemistry and Hematology, University Medical Center Utrecht, 3584 CX Utrecht, Utrecht, the Netherlands
Helen R. Warren
William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UKNIHR Barts Cardiovascular Research Unit, Barts and The London School of Medicine & Dentistry, Queen Mary University, London, London, EC1M 6BQ, UK
Jie Yao
Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, LABiomed at Harbor-UCLA Medical Center, Torrance, CA, USA
Andrianos M. Yiorkas
Section of Investigative Medicine, Department of Medicine, Imperial College London, London, W12 0NN, UKDepartment of Life Sciences, Brunel University London, London, UB8 3PH, UK
Weihua Zhang
Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UKEaling Hospital, London North West Healthcare NHS Trust, Middlesex UB1 3HW, UK
Wei Zhao
Department of Epidemiology, School of Public Health, University of Michigan, 1415 Washington Hgts, Ann Arbor, MI, 48109, USA
Emma Ahlqvist
Lund University Diabetes Centre, Department of Clinical Sciences Malmö, Lund University, Skåne University Hospital, SE-20502 Malmö, Sweden
Mariaelisa Graff
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA
Heather M. Highland
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USAHuman Genetics Center, The University of Texas School of Public Health; The University of Texas Graduate School of Biomedical Sciences at Houston; The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
Anne E Justice
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA
Ken Sin Lo
Montreal Heart Institute, Université de Montréal, Montreal, Quebec, H1T 1C8, Canada
Eirini Marouli
William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK
Carolina Medina-Gomez
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 GE, The NetherlandsDepartment of Internal Medicine, Erasmus University Medical Center, Rotterdam, 3015 GE, the Netherlands
Saima Afaq
Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of Public Health, Imperial College London, London W2 1PG, United Kingdom
Wesam A Alhejily
William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UKDepartment of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
Najaf Amin
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 GE, The Netherlands
Folkert W. Asselbergs
Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, 3584CX Utrecht, The NetherlandsDurrer Center for Cardiovascular Research, Netherlands Heart Institute, 3501DG Utrecht, NetherlandsInstitute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, WC1E 6BT London, United Kingdom
Lori L. Bonnycastle
Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA
Michiel L. Bots
Center for Circulatory Health, University Medical Center Utrecht, 3508GA Utrecht, the Netherlands
Ivan Brandslund
Department of Clinical Biochemistry, Lillebaelt Hospital Vejle, 7100 Vejle, Denmark
Ji Chen
Department of Human Genetics, Wellcome Sanger Institute, Genome Campus, Hinxton, Cambridge, CB10 1SA, UK
Cramer Christensen
Medical Department, Lillebaelt Hospital Vejle, 7100 Vejle, Denmark
John Danesh
Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB18RN, UK
Renée de Mutsert
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, 2333 ZA, the Netherlands
Abbas Dehghan
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 GE, The NetherlandsDepartment of Biostatistics and Epidemiology, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College LondonUK Dementia Research Institute at Imperial College London, London, United Kingdom
Tapani Ebeling
Oulu University Hospital, 90220 Oulu, Finland
Paul Elliott
Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of Public Health, Imperial College London, London W2 1PG, United KingdomImperial College NIHR Biomedical Research Centre, London, United KingdomHealth Data Research UK – London at Imperial College London, United Kingdom
Aliki-Eleni Farmaki
Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, 17671, GreeceDepartment of Population Science and Experimental Medicine, Institute of Cardiovascular Science, University College London, London, UK
Jessica D. Faul
Survey Research Center, Institute for Social Research, University of Michigan, 426 Thompson St, Ann Arbor, MI 48104
Paul W. Franks
Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, SE-205 02, SwedenDepartment of Nutrition, Harvard School of Public Health, Boston, USADivision of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children’s Hospital, Boston, MA 02115
Steve Franks
Institute of Reproductive and Developmental Biology, Imperial College London,W12 0NN London, UK
Andreas Fritsche
Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology, and Clinical Chemistry, University Hospital of Tübingen, Tübingen GermanyGerman Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany
Anette P. Gjesing
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
Mark O. Goodarzi
Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
Vilmundur Gudnason
Icelandic Heart Association, Hotlasmari 1, 201 Kopavogur, IcelandFaculty of Medicine, University of Iceland, 101 Reykjavik, Iceland
Göran Hallmans
Department of Biobank Research, Umeå University, Umeå, SE-901 87, Sweden
Tamara B. Harris
Icelandic Heart Association, Hotlasmari 1, 201 Kopavogur, Iceland
Karl-Heinz Herzig
Institute of Biomedicine and Biocenter of Oulu, Faculty of Medicine, Medical Research Center Oulu and Oulu University Hospital (K.-H.H.), Oulu, FinlandDepartment of Gastroenterology and Metabolism, Poznan University of Medical Sciences, 60-572 Poznan, Poland
Marie-France Hivert
Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, MA, USADiabetes Unit, Massachusetts General Hospital, Boston, MA, USA
Jan-Håkan Jansson
Department of Public Health and Clinical Medicine, Umeå University, Umeå, SE-901 85, Sweden
Min A Jhun
Department of Epidemiology, School of Public Health, University of Michigan, 1415 Washington Hgts, Ann Arbor, MI, 48109, USADivision of Public Health Sciences, Fred Hutchison Cancer Research Center, Seattle, Washington, 98109, USA
Torben Jørgensen
Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, 2000 Frederiksberg, DenmarkDepartment of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, DenmarkFaculty of Medicine, University of Aalborg, 9100 Aalborg, Denmark
Marit E. Jørgensen
Steno Diabetes Center Copenhagen, 2820 Gentofte, DenmarkNational Institute of Public Health, Southern Denmark University, 5000 Odense, Denmark
Pekka Jousilahti
Department of Public Health Solutions, National Institute for Health and Welfare, FI-00271 Helsinki, Finland
Eero Kajantie
PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, FinlandDepartment of Public Health Solutions, National Institute for Health and Welfare, FI-00271 Helsinki, FinlandNorwegian University of Science and Technology, Department of Clinical and Molecular Medicine, Trondheim, NorwayChildren’s Hospital, Helsinki University Hospital and University of Helsinki
Maria Karaleftheri
Echinos Medical Centre, Echinos, Greece
Sharon L.R. Kardia
Department of Epidemiology, School of Public Health, University of Michigan, 1415 Washington Hgts, Ann Arbor, MI, 48109, USA
Leena Kinnunen
Department of Public Health Solutions, National Institute for Health and Welfare, FI-00271 Helsinki, Finland
Heikki A. Koistinen
Department of Public Health Solutions, National Institute for Health and Welfare, FI-00271 Helsinki, FinlandUniversity of Helsinki and Department of Medicine, Helsinki University Central Hospital, P.O.Box 340, Haartmaninkatu 4, Helsinki, FI-00029, FinlandMinerva Foundation Institute for Medical Research, Biomedicum 2U Helsinki, Tukholmankatu 8, FI-00290 Helsinki, Finland
Pirjo Komulainen
Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, 70100 Kuopio, Finland
Peter Kovacs
Integrated Research and Treatment (IFB) Center AdiposityDiseases, University of Leipzig, Liebigstrasse 19-21, 04103 Leipzig, GermanyDepartment of Medicine, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany
Johanna Kuusisto
Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, 70210 Kuopio, Finland
Markku Laakso
Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, 70210 Kuopio, Finland
Leslie A. Lange
Department of Medicine, Division of Bioinformatics and Personalized Medicine, University of Colorado Denver, Aurora, CO, USA
Lenore J. Launer
Icelandic Heart Association, Hotlasmari 1, 201 Kopavogur, IcelandDepartment of Public Health Solutions, National Institute for Health and Welfare, FI-00271 Helsinki, Finland
Jung-Jin Lee
Department of Biostatistics and Epidemiology, University of Pennsylvania, USA, 19104
Aaron Leong
Division of General Internal Medicine, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Boston, MA, USA
Jaana Lindström
Department of Public Health Solutions, National Institute for Health and Welfare, FI-00271 Helsinki, Finland
Jocelyn E. Manning Fox
Alberta Diabetes Institute IsletCore, University of Alberta, Edmonton, Canada, T6G 2E1Department of Pharmacology, University of Alberta, Edmonton, Canada, T6G 2E1
Satu Männistö
Department of Public Health Solutions, National Institute for Health and Welfare, FI-00271 Helsinki, Finland
Nisa M Maruthur
Department of Medicine, Division of General Internal Medicine, The Johns Hopkins University School of Medicine, Baltimore, MarylandWelch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USADepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Leena Moilanen
Kuopio University Hospital, 70210 Kuopio, Finland
Antonella Mulas
Italian National Research Council, Institute of Genetics and Biomedic Research, Cittadella Universitaria, Monserrato (CA) 09042, ItalyDipartimento di Scienze Biomediche, Università degli Studi di Sassari, 07100 Sassari, Italy
Mike A. Nalls
Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, 20892, USAData Tecnica International, LLC, Glen Echo, Maryland 20812, USA
Matthew Neville
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LE
James S. Pankow
Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, 55455, USA
Alison Pattie
Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ
Eva R.B. Petersen
Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, 5000 Odense, Denmark
Hannu Puolijoki
South Ostobothnia Central Hospital, 60220 Seinajoki, Finland
Asif Rasheed
Center for Non-Communicable Diseases, Karachi, Pakistan
Paul Redmond
Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ
Frida Renström
Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, SE-205 02, SwedenDepartment of Biobank Research, Umeå University, Umeå, SE-901 87, Sweden
Michael Roden
Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, GermanyDivision of Endocrinology and Diabetology, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, GermanyGerman Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany
Danish Saleheen
Department of Biostatistics and Epidemiology, University of Pennsylvania, USA, 19104Center for Non-Communicable Diseases, Karachi, Pakistan
Juha Saltevo
Central Finland Central Hospital, 40620 Jyvaskyla, Finland
Kai Savonen
Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, 70100 Kuopio, FinlandDepartment of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, 70029 Kuopio, Finland
Sylvain Sebert
Faculty of Medicine, Center for Life Course Health Research, University of Oulu, Oulu, FinlandBiocenter Oulu, University of Oulu, Oulu, Finland
Tea Skaaby
Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, 2000 Frederiksberg, Denmark
Kerrin S Small
Department of Twin Research and Genetic Epidemiology, King’s College London, London,, SE1 7EH, UK
Alena Stančáková
Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, 70210 Kuopio, Finland
Jakob Stokholm
COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital 2820, University of Copenhagen, Copenhagen, Denmark
Konstantin Strauch
Institute of Genetic Epidemiology, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany, German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
E-Shyong Tai
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, Singapore 119228Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore 117549, SingaporeDuke-NUS Medical School, Singapore, 8 College Road, Singapore 169857
Kent D. Taylor
Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, LABiomed at Harbor-UCLA Medical Center, Torrance, CA, USA
Betina H. Thuesen
Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, 2000 Frederiksberg, Denmark
Anke Tönjes
Department of Medicine, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany
Emmanouil Tsafantakis
Anogia Medical Centre, Anogia, Greece
Tiinamaija Tuomi
Folkhälsan Research Centre, Helsinki, FinlandDepartment of Endocrinology, Helsinki University Central Hospital, Helsinki, FinlandInstitute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland
Jaakko Tuomilehto
Department of Public Health Solutions, National Institute for Health and Welfare, FI-00271 Helsinki, FinlandDepartment of Public Health, University of Helsinki, Helsinki, FinlandDepartment of Neuroscience and Preventive Medicine, Danube-University Krems, 3500 Krems, AustriaSaudi Diabetes Research Group, King Abdulaziz University, 21589 Jeddah, Saudi Arabia
Matti Uusitupa
Department of Public Health and Clinical Nutrition, University of Eastern Finland, 70210 Kuopio, Finland
Marja Vääräsmäki
PEDEGO Research Unit (Research Unit for Pediatrics, Dermatology, Clinical Genetics, Obstetrics and Gynecology), Medical Research Center Oulu (MRC Oulu), Oulu University Hospital and University of Oulu, Oulu, FinlandDepartment of Welfare, Children, Adolescents and Families Unit, National Institute for Health and Welfare, Oulu, Finland
Ilonca Vaartjes
Center for Circulatory Health, University Medical Center Utrecht, 3508GA Utrecht, the Netherlands
Magdalena Zoledziewska
Italian National Research Council, Institute of Genetics and Biomedic Research, Cittadella Universitaria, Monserrato (CA) 09042, Italy
Goncalo Abecasis
Center for Statistical Genetics, University of Michigan, 1415 Washington Heights, 48109 Ann Arbor, MI, USA
Beverley Balkau
INSERM U1018, Centre de recherche en Épidémiologie et Santé des Populations (CESP), Villejuif, France
Hans Bisgaard
COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital 2820, University of Copenhagen, Copenhagen, Denmark
Alexandra I. Blakemore
Department of Life Sciences, Brunel University London, London, UB8 3PH, UKSection of Investigative Medicine, Department of Medicine, Imperial College London, London, W12 0NN, UK
Matthias Blüher
Integrated Research and Treatment (IFB) Center AdiposityDiseases, University of Leipzig, Liebigstrasse 19-21, 04103 Leipzig, GermanyDepartment of Medicine, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany
Heiner Boeing
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), 14558 Nuthetal, Germany
Eric Boerwinkle
The Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, 77030, USA
Klaus Bønnelykke
COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital 2820, University of Copenhagen, Copenhagen, Denmark
Erwin P. Bottinger
The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY, 10069, USA
Mark J. Caulfield
William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UKNIHR Barts Cardiovascular Research Unit, Barts and The London School of Medicine & Dentistry, Queen Mary University, London, London, EC1M 6BQ, UK
John C Chambers
Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of Public Health, Imperial College London, London W2 1PG, United KingdomEaling Hospital, London North West Healthcare NHS Trust, Middlesex UB1 3HW, UKImperial College Healthcare NHS Trust, London W12 0HS, UK
Daniel I Chasman
Division of Preventive Medicine, Brigham and Women’s Hospital, Boston MA, 02215, USAHarvard School of Medicine, Boston MA, 02115, USADivision of Genetics, Brigham and Women’s Hospital and Harvard Medical School, Boston MA, USA
Ching-Yu Cheng
Singapore Eye Research Institute, Singapore National Eye Centre, The Academia, 20 College Road, Singapore 169856Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, 8 College Road, Singapore 169857Department of Ophthalmology, Yong Loo Lin School of Medicine,National University of Singapore, Singapore, 1E Kent Ridge Rd, Singapore 119228
Anne Clark
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LE
Francis S. Collins
Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA
Josef Coresh
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USAWelch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA
Francesco Cucca
Italian National Research Council, Institute of Genetics and Biomedic Research, Cittadella Universitaria, Monserrato (CA) 09042, ItalyDipartimento di Scienze Biomediche, Università degli Studi di Sassari, 07100 Sassari, Italy
Gert J. de Borst
Department of Vascular Surgery; Division of Surgical Specialties; University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands
Ian J. Deary
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZDepartment of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ
George Dedoussis
Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, 17671, Greece
Panos Deloukas
William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UKPrincess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia
Hester M. den Ruijter
Experimental Cardiology Laboratory, Division Heart and Lungs, University Medical Center Utrecht, 3584 CX Utrecht, Utrecht, the Netherlands
Josée Dupuis
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USANational Heart, Lung, and Blood Institute (NHLBI) Framingham Heart Study, Framingham, MA, USA
Michele K. Evans
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
Ele Ferrannini
CNR Institute of Clinical Physiology, Pisa, Italy, Department of Clinical & Experimental Medicine, University of Pisa, Italy
Oscar H Franco
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 GE, The NetherlandsInstitute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland
Harald Grallert
Institute of Epidemiology II, Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, GermanGerman Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany
Leif Groop
Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Malmö, SwedenInstitute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland
Torben Hansen
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, DenmarkFaculty of Health Sciences, University of Southern Denmark, 5000 Odense, Denmark
Andrew T. Hattersley
University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK
Caroline Hayward
Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK
Joel N. Hirschhorn
Departments of Pediatrics and Genetics, Harvard Medical School, Boston, MA 02115Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children’s Hospital, Boston, MA 02115Broad Institute of MIT and Harvard, Cambridge, MA, 02142
Arfan Ikram
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 GE, The Netherlands
Erik Ingelsson
Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USADepartment of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, 75237, SwedenStanford Cardiovascular Institute, Stanford University, Stanford, CA 94305Stanford Diabetes Research Center, Stanford University, Stanford, CA 94305
Fredrik Karpe
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LEOxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK, OX3 7LE
Kay-Tee Kaw
Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Strangeways Research Laboratory, Cambridge, CB1 8RN, UK
Wieland Kiess
Pediatric Research Center, Department of Women & Child Health, University of Leipzig, Leipzig, Germany
Jaspal S Kooner
National Heart and Lung Institute, Imperial College London, London W12 0NN, UKEaling Hospital, London North West Healthcare NHS Trust, Middlesex UB1 3HW, UKImperial College Healthcare NHS Trust, London W12 0HS, UK
Antje Körner
Pediatric Research Center, Department of Women & Child Health, University of Leipzig, Leipzig, Germany
Timo Lakka
Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio Campus, 70211 Kuopio, FinlandFoundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, 70100 Kuopio, FinlandDepartment of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, 70029 Kuopio, Finland
Claudia Langenberg
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
Lars Lind
Department of Medical Sciences, Molecular Epidemiology; EpiHealth, Uppsala University, Uppsala, 75185, Sweden
Cecilia M Lindgren
Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK, OX3 7BNThe Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7BN, UK
Allan Linneberg
Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, 2000 Frederiksberg, DenmarkDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
Leonard Lipovich
Center for Molecular Medicine and Genetics, Wayne State University, 540 E. Canfield St., 3208 Scott Hall, Detroit, Michigan 48201-1928, U.S.A.Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA
Ching-Ti Liu
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
Jun Liu
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 GE, The Netherlands
Yongmei Liu
Department of Epidemiology & Prevention, Division of Public Health Sciences, Wake Forest University, Winston-Salem, NC, 27157, USA
Ruth J.F. Loos
The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY, 10069, USAThe Mindich Child Health and Development Institute, The Icahn School of Medicine at Mount Sinai, New York, NY, 10069, USA
Patrick E. MacDonald
Alberta Diabetes Institute IsletCore, University of Alberta, Edmonton, Canada, T6G 2E1Department of Pharmacology, University of Alberta, Edmonton, Canada, T6G 2E1
Karen L. Mohlke
Department of Genetics, University of North Carolina, Chapel Hill, NC, 27599, USA
Andrew D Morris
Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH16 4UX, UK
Patricia B. Munroe
William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UKNIHR Barts Cardiovascular Research Unit, Barts and The London School of Medicine & Dentistry, Queen Mary University, London, London, EC1M 6BQ, UK
Alison Murray
Aberdeen Biomedical Imaging Centre, University of Aberdeen, Foresterhill Health Campus, Aberdeen, AB25 2ZD
Sandosh Padmanabhan
British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK
Colin N A Palmer
Division of Population Health and Genomics, School of Medicine, University of Dundee, DUNEE DD2 4BF
Gerard Pasterkamp
Experimental Cardiology Laboratory, Division Heart and Lungs, University Medical Center Utrecht, 3584 CX Utrecht, Utrecht, the NetherlandsLaboratory of Clinical Chemistry and Hematology, University Medical Center Utrecht, 3584 CX Utrecht, Utrecht, the Netherlands
Oluf Pedersen
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
Patricia A. Peyser
Department of Epidemiology, School of Public Health, University of Michigan, 1415 Washington Hgts, Ann Arbor, MI, 48109, USA
Ozren Polasek
Faculty of Medicine, University of Split, Split, Croatia
David Porteous
Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK
Michael A. Province
Department of Genetics, Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri 63108, USA
Bruce M Psaty
Cardiovascular Health Research Unit, University of Washington, 1730 Minor Ave. Suite 1360, Seattle, WA 98101, USADepartment of Medicine, University of Washington, Seattle, WA, USADepartments of Epidemiology and Health Services, University of Washington, Seattle, WA, USAKaiser Permanent Washington Health Research Institute, Seattle, WA, USA
Rainer Rauramaa
Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, 70100 Kuopio, Finland
Paul M Ridker
Division of Preventive Medicine, Brigham and Women’s Hospital, Boston MA, 02215, USAHarvard School of Medicine, Boston MA, 02115, USADivision of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston MA 02115
Olov Rolandsson
Department of Public Health & Clinical Medicine, Section for Family Medicine, Umeå University, Umeå, SE-901 85, Sweden
Patrik Rorsman
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LEOxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK, OX3 7LE
Frits R. Rosendaal
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, 2333 ZA, the Netherlands
Igor Rudan
Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH16 4UX, UK
Veikko Salomaa
Department of Public Health Solutions, National Institute for Health and Welfare, FI-00271 Helsinki, Finland
Matthias B. Schulze
Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, GermanyGerman Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany
Robert Sladek
Department of Medicine, McGill University, Montreal (Quebec) Canada H4A 3J1Department of Human Genetics, McGill University, Montreal (Quebec) Canada H3A 1B1
Blair H Smith
Division of Population Health and Genomics, School of Medicine, University of Dundee, DUNEE DD2 4BF
Timothy D Spector
Department of Twin Research and Genetic Epidemiology, King’s College London, London,, SE1 7EH, UK
John M. Starr
Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, EH8 9JZCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ
Michael Stumvoll
Department of Medicine, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany
Cornelia M van Duijn
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 GE, The Netherlands
Mark Walker
Institute of Cellular Medicine, The Medical School, Newcastle University, Newcastle, NE2 4HH, UK
Nick J. Wareham
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
David R. Weir
Survey Research Center, Institute for Social Research, University of Michigan, 426 Thompson St, Ann Arbor, MI 48104
James G. Wilson
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA
Tien Yin Wong
Singapore Eye Research Institute, Singapore National Eye Centre, The Academia, 20 College Road, Singapore 169856Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, 8 College Road, Singapore 169857Department of Ophthalmology, Yong Loo Lin School of Medicine,National University of Singapore, Singapore, 1E Kent Ridge Rd, Singapore 119228
Eleftheria Zeggini
Department of Human Genetics, Wellcome Sanger Institute, Genome Campus, Hinxton, Cambridge, CB10 1SA, UKInstitute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
Alan B. Zonderman
Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
Jerome I. Rotter
Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, LABiomed at Harbor-UCLA Medical Center, Torrance, CA, USA
Andrew P. Morris
Department of Biostatistics, University of Liverpool, Liverpool L69 3GL, UKWellcome Centre for Human Genetics, University of Oxford, Oxford, UK, OX3 7BN
Michael Boehnke
Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA
Jose Florez
Diabetes Unit, Department of Medicine, Massachusetts General, Boston, MA, USAProgram in Medical Genetics, Broad Institute, Cambridge, MA, USA
Mark I McCarthy
Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK, OX3 7BNOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LEOxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK, OX3 7LE
James B Meigs
Division of General Internal Medicine, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Boston, MA, USAProgram in Medical Genetics, Broad Institute, Cambridge, MA, USA
Anubha Mahajan
Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK, OX3 7BN
Robert A. Scott
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
Anna L Gloyn
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LEWellcome Centre for Human Genetics, University of Oxford, Oxford, UK, OX3 7BNOxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK, OX3 7LE
Inês Barroso
Department of Human Genetics, Wellcome Sanger Institute, Genome Campus, Hinxton, Cambridge, CB10 1SA, UKMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
Summary
Metabolic dysregulation in multiple tissues alters glucose homeostasis and influences risk for type 2 diabetes (T2D). To identify pathways and tissues influencing T2D-relevant glycemic traits (fasting glucose [FG], fasting insulin [FI], two-hour glucose [2hGlu] and glycated hemoglobin [HbA1c]), we investigated associations of exome-array variants in up to 144,060 individuals without diabetes of multiple ancestries. Single-variant analyses identified novel associations at 21 coding variants in 18 novel loci, whilst gene-based tests revealed signals at two genes, TF (HbA1c) and G6PC (FG, FI). Pathway and tissue enrichment analyses of trait-associated transcripts confirmed the importance of liver and kidney for FI and pancreatic islets for FG regulation, implicated adipose tissue in FI and the gut in 2hGlu, and suggested a role for the non-endocrine pancreas in glucose homeostasis. Functional studies demonstrated that a novel FG/FI association at the liver-enriched G6PC transcript was driven by multiple rare loss-of-function variants. The FG/HbA1c-associated, islet-specific G6PC2 transcript also contained multiple rare functional variants, including two alleles within the same codon with divergent effects on glucose levels. Our findings highlight the value of integrating genomic and functional data to maximize biological inference.
Highlights
23 novel coding variant associations (single-point and gene-based) for glycemic traits
51 effector transcripts highlighted different pathway/tissue signatures for each trait
The exocrine pancreas and gut influence fasting and 2h glucose, respectively
Multiple variants in liver-enriched G6PC and islet-specific G6PC2 influence glycemia
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Posted October 03, 2019.
Tissue-Specific Alteration of Metabolic Pathways Influences Glycemic Regulation
Natasha H. J. Ng, Sara M. Willems, Juan Fernandez, Rebecca S. Fine, Eleanor Wheeler, Jennifer Wessel, Hidetoshi Kitajima, Gaelle Marenne, Jana K. Rundle, Xueling Sim, Hanieh Yeghootkar, Nicola L. Beer, Anne Raimondo, Andrei I. Tarasov, Soren K. Thomsen, Martijn van de Bunt, Shuai Wang, Sai Chen, Yuning Chen, Yii-Der Ida Chen, Hugoline G. de Haan, Niels Grarup, Ruifang Li-Gao, Tibor V. Varga, Jennifer L Asimit, Shuang Feng, Rona J. Strawbridge, Erica L. Kleinbrink, Tarunveer S. Ahluwalia, Ping An, Emil V. Appel, Dan E Arking, Juha Auvinen, Lawrence F. Bielak, Nathan A. Bihlmeyer, Jette Bork-Jensen, Jennifer A. Brody, Archie Campbell, Audrey Y Chu, Gail Davies, Ayse Demirkan, James S. Floyd, Franco Giulianini, Xiuqing Guo, Stefan Gustafsson, Benoit Hastoy, Anne U. Jackson, Johanna Jakobsdottir, Marjo-Riitta Jarvelin, Richard A. Jensen, Stavroula Kanoni, Sirkka Keinanen-Kiukaanniemi, Jin Li, Man Li, Kurt Lohman, Yingchang Lu, Jian’an Luan, Alisa K. Manning, Jonathan Marten, Carola Marzi, Karina Meidtner, Dennis O. Mook-Kanamori, Taulant Muka, Giorgio Pistis, Bram Prins, Kenneth M. Rice, Neil Robertson, Serena Sanna, Yuan Shi, Albert Vernon Smith, Jennifer A. Smith, Lorraine Southam, Heather M. Stringham, Salman M. Tajuddin, Vinicius Tragante, Sander W. van der Laan, Helen R. Warren, Jie Yao, Andrianos M. Yiorkas, Weihua Zhang, Wei Zhao, Emma Ahlqvist, Mariaelisa Graff, Heather M. Highland, Anne E Justice, Ken Sin Lo, Eirini Marouli, Carolina Medina-Gomez, Saima Afaq, Wesam A Alhejily, Najaf Amin, Folkert W. Asselbergs, Lori L. Bonnycastle, Michiel L. Bots, Ivan Brandslund, Ji Chen, Cramer Christensen, John Danesh, Renée de Mutsert, Abbas Dehghan, Tapani Ebeling, Paul Elliott, EPIC-InterAct Consortium, Aliki-Eleni Farmaki, Jessica D. Faul, Paul W. Franks, Steve Franks, Andreas Fritsche, Anette P. Gjesing, Mark O. Goodarzi, Vilmundur Gudnason, Göran Hallmans, Tamara B. Harris, Karl-Heinz Herzig, Marie-France Hivert, Jan-Håkan Jansson, Min A Jhun, Torben Jørgensen, Marit E. Jørgensen, Pekka Jousilahti, Eero Kajantie, Maria Karaleftheri, Sharon L.R. Kardia, Leena Kinnunen, Heikki A. Koistinen, Pirjo Komulainen, Peter Kovacs, Johanna Kuusisto, Markku Laakso, Leslie A. Lange, Lenore J. Launer, Jung-Jin Lee, Aaron Leong, Jaana Lindström, Jocelyn E. Manning Fox, Satu Männistö, Nisa M Maruthur, Leena Moilanen, Antonella Mulas, Mike A. Nalls, Matthew Neville, James S. Pankow, Alison Pattie, Eva R.B. Petersen, Hannu Puolijoki, Asif Rasheed, Paul Redmond, Frida Renström, Michael Roden, Danish Saleheen, Juha Saltevo, Kai Savonen, Sylvain Sebert, Tea Skaaby, Kerrin S Small, Alena Stančáková, Jakob Stokholm, Konstantin Strauch, E-Shyong Tai, Kent D. Taylor, Betina H. Thuesen, Anke Tönjes, Emmanouil Tsafantakis, Tiinamaija Tuomi, Jaakko Tuomilehto, Understanding Society Scientific Group, Matti Uusitupa, Marja Vääräsmäki, Ilonca Vaartjes, Magdalena Zoledziewska, Goncalo Abecasis, Beverley Balkau, Hans Bisgaard, Alexandra I. Blakemore, Matthias Blüher, Heiner Boeing, Eric Boerwinkle, Klaus Bønnelykke, Erwin P. Bottinger, Mark J. Caulfield, John C Chambers, Daniel I Chasman, Ching-Yu Cheng, Anne Clark, Francis S. Collins, Josef Coresh, Francesco Cucca, Gert J. de Borst, Ian J. Deary, George Dedoussis, Panos Deloukas, Hester M. den Ruijter, Josée Dupuis, Michele K. Evans, Ele Ferrannini, Oscar H Franco, Harald Grallert, Leif Groop, Torben Hansen, Andrew T. Hattersley, Caroline Hayward, Joel N. Hirschhorn, Arfan Ikram, Erik Ingelsson, Fredrik Karpe, Kay-Tee Kaw, Wieland Kiess, Jaspal S Kooner, Antje Körner, Timo Lakka, Claudia Langenberg, Lars Lind, Cecilia M Lindgren, Allan Linneberg, Leonard Lipovich, Ching-Ti Liu, Jun Liu, Yongmei Liu, Ruth J.F. Loos, Patrick E. MacDonald, Karen L. Mohlke, Andrew D Morris, Patricia B. Munroe, Alison Murray, Sandosh Padmanabhan, Colin N A Palmer, Gerard Pasterkamp, Oluf Pedersen, Patricia A. Peyser, Ozren Polasek, David Porteous, Michael A. Province, Bruce M Psaty, Rainer Rauramaa, Paul M Ridker, Olov Rolandsson, Patrik Rorsman, Frits R. Rosendaal, Igor Rudan, Veikko Salomaa, Matthias B. Schulze, Robert Sladek, Blair H Smith, Timothy D Spector, John M. Starr, Michael Stumvoll, Cornelia M van Duijn, Mark Walker, Nick J. Wareham, David R. Weir, James G. Wilson, Tien Yin Wong, Eleftheria Zeggini, Alan B. Zonderman, Jerome I. Rotter, Andrew P. Morris, Michael Boehnke, Jose Florez, Mark I McCarthy, James B Meigs, Anubha Mahajan, Robert A. Scott, Anna L Gloyn, Inês Barroso
bioRxiv 790618; doi: https://doi.org/10.1101/790618
Tissue-Specific Alteration of Metabolic Pathways Influences Glycemic Regulation
Natasha H. J. Ng, Sara M. Willems, Juan Fernandez, Rebecca S. Fine, Eleanor Wheeler, Jennifer Wessel, Hidetoshi Kitajima, Gaelle Marenne, Jana K. Rundle, Xueling Sim, Hanieh Yeghootkar, Nicola L. Beer, Anne Raimondo, Andrei I. Tarasov, Soren K. Thomsen, Martijn van de Bunt, Shuai Wang, Sai Chen, Yuning Chen, Yii-Der Ida Chen, Hugoline G. de Haan, Niels Grarup, Ruifang Li-Gao, Tibor V. Varga, Jennifer L Asimit, Shuang Feng, Rona J. Strawbridge, Erica L. Kleinbrink, Tarunveer S. Ahluwalia, Ping An, Emil V. Appel, Dan E Arking, Juha Auvinen, Lawrence F. Bielak, Nathan A. Bihlmeyer, Jette Bork-Jensen, Jennifer A. Brody, Archie Campbell, Audrey Y Chu, Gail Davies, Ayse Demirkan, James S. Floyd, Franco Giulianini, Xiuqing Guo, Stefan Gustafsson, Benoit Hastoy, Anne U. Jackson, Johanna Jakobsdottir, Marjo-Riitta Jarvelin, Richard A. Jensen, Stavroula Kanoni, Sirkka Keinanen-Kiukaanniemi, Jin Li, Man Li, Kurt Lohman, Yingchang Lu, Jian’an Luan, Alisa K. Manning, Jonathan Marten, Carola Marzi, Karina Meidtner, Dennis O. Mook-Kanamori, Taulant Muka, Giorgio Pistis, Bram Prins, Kenneth M. Rice, Neil Robertson, Serena Sanna, Yuan Shi, Albert Vernon Smith, Jennifer A. Smith, Lorraine Southam, Heather M. Stringham, Salman M. Tajuddin, Vinicius Tragante, Sander W. van der Laan, Helen R. Warren, Jie Yao, Andrianos M. Yiorkas, Weihua Zhang, Wei Zhao, Emma Ahlqvist, Mariaelisa Graff, Heather M. Highland, Anne E Justice, Ken Sin Lo, Eirini Marouli, Carolina Medina-Gomez, Saima Afaq, Wesam A Alhejily, Najaf Amin, Folkert W. Asselbergs, Lori L. Bonnycastle, Michiel L. Bots, Ivan Brandslund, Ji Chen, Cramer Christensen, John Danesh, Renée de Mutsert, Abbas Dehghan, Tapani Ebeling, Paul Elliott, EPIC-InterAct Consortium, Aliki-Eleni Farmaki, Jessica D. Faul, Paul W. Franks, Steve Franks, Andreas Fritsche, Anette P. Gjesing, Mark O. Goodarzi, Vilmundur Gudnason, Göran Hallmans, Tamara B. Harris, Karl-Heinz Herzig, Marie-France Hivert, Jan-Håkan Jansson, Min A Jhun, Torben Jørgensen, Marit E. Jørgensen, Pekka Jousilahti, Eero Kajantie, Maria Karaleftheri, Sharon L.R. Kardia, Leena Kinnunen, Heikki A. Koistinen, Pirjo Komulainen, Peter Kovacs, Johanna Kuusisto, Markku Laakso, Leslie A. Lange, Lenore J. Launer, Jung-Jin Lee, Aaron Leong, Jaana Lindström, Jocelyn E. Manning Fox, Satu Männistö, Nisa M Maruthur, Leena Moilanen, Antonella Mulas, Mike A. Nalls, Matthew Neville, James S. Pankow, Alison Pattie, Eva R.B. Petersen, Hannu Puolijoki, Asif Rasheed, Paul Redmond, Frida Renström, Michael Roden, Danish Saleheen, Juha Saltevo, Kai Savonen, Sylvain Sebert, Tea Skaaby, Kerrin S Small, Alena Stančáková, Jakob Stokholm, Konstantin Strauch, E-Shyong Tai, Kent D. Taylor, Betina H. Thuesen, Anke Tönjes, Emmanouil Tsafantakis, Tiinamaija Tuomi, Jaakko Tuomilehto, Understanding Society Scientific Group, Matti Uusitupa, Marja Vääräsmäki, Ilonca Vaartjes, Magdalena Zoledziewska, Goncalo Abecasis, Beverley Balkau, Hans Bisgaard, Alexandra I. Blakemore, Matthias Blüher, Heiner Boeing, Eric Boerwinkle, Klaus Bønnelykke, Erwin P. Bottinger, Mark J. Caulfield, John C Chambers, Daniel I Chasman, Ching-Yu Cheng, Anne Clark, Francis S. Collins, Josef Coresh, Francesco Cucca, Gert J. de Borst, Ian J. Deary, George Dedoussis, Panos Deloukas, Hester M. den Ruijter, Josée Dupuis, Michele K. Evans, Ele Ferrannini, Oscar H Franco, Harald Grallert, Leif Groop, Torben Hansen, Andrew T. Hattersley, Caroline Hayward, Joel N. Hirschhorn, Arfan Ikram, Erik Ingelsson, Fredrik Karpe, Kay-Tee Kaw, Wieland Kiess, Jaspal S Kooner, Antje Körner, Timo Lakka, Claudia Langenberg, Lars Lind, Cecilia M Lindgren, Allan Linneberg, Leonard Lipovich, Ching-Ti Liu, Jun Liu, Yongmei Liu, Ruth J.F. Loos, Patrick E. MacDonald, Karen L. Mohlke, Andrew D Morris, Patricia B. Munroe, Alison Murray, Sandosh Padmanabhan, Colin N A Palmer, Gerard Pasterkamp, Oluf Pedersen, Patricia A. Peyser, Ozren Polasek, David Porteous, Michael A. Province, Bruce M Psaty, Rainer Rauramaa, Paul M Ridker, Olov Rolandsson, Patrik Rorsman, Frits R. Rosendaal, Igor Rudan, Veikko Salomaa, Matthias B. Schulze, Robert Sladek, Blair H Smith, Timothy D Spector, John M. Starr, Michael Stumvoll, Cornelia M van Duijn, Mark Walker, Nick J. Wareham, David R. Weir, James G. Wilson, Tien Yin Wong, Eleftheria Zeggini, Alan B. Zonderman, Jerome I. Rotter, Andrew P. Morris, Michael Boehnke, Jose Florez, Mark I McCarthy, James B Meigs, Anubha Mahajan, Robert A. Scott, Anna L Gloyn, Inês Barroso
bioRxiv 790618; doi: https://doi.org/10.1101/790618
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