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
1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LE
2Stem Cells and Diabetes Laboratory, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore
Sara M. Willems
3MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
Juan Fernandez
4Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK, OX3 7BN
Rebecca S. Fine
5Department of Genetics, Harvard Medical School, Boston, MA, 02115
6Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children’s Hospital, Boston, MA 02115
7Broad Institute of MIT and Harvard, Cambridge, MA, 02142
Eleanor Wheeler
8Department of Human Genetics, Wellcome Sanger Institute, Genome Campus, Hinxton, Cambridge, CB10 1SA, UK
3MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
Jennifer Wessel
9Departments of Epidemiology & Medicine, Schools of Public Health & Medicine, Indiana University, Indiaiapolis, IN 46202
10Diabetes Translational Research Center, Indiana University School of Medicine, Indianapolis, IN 46202
Hidetoshi Kitajima
4Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK, OX3 7BN
Gaelle Marenne
8Department of Human Genetics, Wellcome Sanger Institute, Genome Campus, Hinxton, Cambridge, CB10 1SA, UK
Jana K. Rundle
1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LE
Xueling Sim
11Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore 117549, Singapore
12Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA
Hanieh Yeghootkar
13Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK
Nicola L. Beer
1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LE
Anne Raimondo
1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LE
Andrei I. Tarasov
1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LE
Soren K. Thomsen
1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LE
14Vertex Pharmaceuticals Europe Ltd, Milton Park, Abingdon, OX14 4RW, UK
Martijn van de Bunt
4Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK, OX3 7BN
1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LE
Shuai Wang
15Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
Sai Chen
12Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA
Yuning Chen
15Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
Yii-Der Ida Chen
16Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, LABiomed at Harbor-UCLA Medical Center, Torrance, CA, USA
Hugoline G. de Haan
17Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, 2333 ZA, the Netherlands
Niels Grarup
18Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
Ruifang Li-Gao
17Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, 2333 ZA, the Netherlands
Tibor V. Varga
19Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, SE-205 02, Sweden
Jennifer L Asimit
8Department of Human Genetics, Wellcome Sanger Institute, Genome Campus, Hinxton, Cambridge, CB10 1SA, UK
20MRC Biostatistics Unit, Cambridge Biomedical Campus, Cambridge Institute of Public Health, Forvie Site, Robinson Way, Cambridge CB2 0SR, UK
Shuang Feng
21Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
Rona J. Strawbridge
22UKRI 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 8RZ
23Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm,171 76, Sweden
Erica L. Kleinbrink
24Center 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
25COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital 2820, University of Copenhagen, Copenhagen, Denmark
26Steno Diabetes Center Copenhagen, 2820 Gentofte, Denmark
Ping An
27Department of Genetics, Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri 63108, USA
Emil V. Appel
18Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
Dan E Arking
28McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Juha Auvinen
29Center for Life Course Health Research, University of Oulu, PO Box 8000, 90014 Oulu, Finland
30Unit of Primary Care, Oulu University Hospital, Oulu, Finland
Lawrence F. Bielak
31Department of Epidemiology, School of Public Health, University of Michigan, 1415 Washington Hgts, Ann Arbor, MI, 48109, USA
Nathan A. Bihlmeyer
28McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Jette Bork-Jensen
18Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
Jennifer A. Brody
32Cardiovascular Health Research Unit, University of Washington, 1730 Minor Ave. Suite 1360, Seattle, WA 98101, USA
33Department of Medicine, University of Washington, Seattle, WA, USA
Archie Campbell
34Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK
Audrey Y Chu
35Division of Preventive Medicine, Brigham and Women’s Hospital, Boston MA, 02215, USA
Gail Davies
36Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ
37Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ
Ayse Demirkan
38Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 GE, The Netherlands
James S. Floyd
32Cardiovascular Health Research Unit, University of Washington, 1730 Minor Ave. Suite 1360, Seattle, WA 98101, USA
33Department of Medicine, University of Washington, Seattle, WA, USA
Franco Giulianini
35Division of Preventive Medicine, Brigham and Women’s Hospital, Boston MA, 02215, USA
Xiuqing Guo
16Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, LABiomed at Harbor-UCLA Medical Center, Torrance, CA, USA
Stefan Gustafsson
39Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, 75237, Sweden
Benoit Hastoy
1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LE
Anne U. Jackson
12Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA
Johanna Jakobsdottir
40Icelandic Heart Association, Hotlasmari 1, 201 Kopavogur, Iceland
Marjo-Riitta Jarvelin
41Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of Public Health, Imperial College London, London W2 1PG, United Kingdom
29Center for Life Course Health Research, University of Oulu, PO Box 8000, 90014 Oulu, Finland
42Biocenter Oulu, University of Oulu, Oulu, Finland
Richard A. Jensen
32Cardiovascular Health Research Unit, University of Washington, 1730 Minor Ave. Suite 1360, Seattle, WA 98101, USA
33Department of Medicine, University of Washington, Seattle, WA, USA
Stavroula Kanoni
43William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK
Sirkka Keinanen-Kiukaanniemi
44Faculty of Medicine, Center for Life Course Health Research, University of Oulu, Oulu, Finland
45MRC and Unit of Primary Care, Oulu University Hospital, Oulu, Finland
Jin Li
46Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
Man Li
47Division of Nephrology, Internal Medicine, School of Medicine, University of Utah, Salt Lake City, Utah
48Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Kurt Lohman
49Department of Biostatistical Sciences, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157
Yingchang Lu
50The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY, 10069, USA
51Department of Medicine, Division of Epidemiology, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine Nashville, TN 37203 USA
Jian’an Luan
3MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
Alisa K. Manning
52Center for Human Genetics Research, Massachusetts General Hospital, Boston, MA, 02114, USA
53Department of Medicine, Harvard Medical School, Boston, MA, USA
Jonathan Marten
54Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK
Carola Marzi
55Institute of Epidemiology II, Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German
56German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany
Karina Meidtner
57Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany
56German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany
Dennis O. Mook-Kanamori
17Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, 2333 ZA, the Netherlands
58Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, 2333 ZA, the Netherlands
Taulant Muka
59Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland
38Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 GE, The Netherlands
Giorgio Pistis
60Italian National Research Council, Institute of Genetics and Biomedic Research, Cittadella Universitaria, Monserrato (CA) 09042, Italy
61Center for Statistical Genetics, University of Michigan, 1415 Washington Heights, 48109 Ann Arbor, MI, USA
Bram Prins
8Department of Human Genetics, Wellcome Sanger Institute, Genome Campus, Hinxton, Cambridge, CB10 1SA, UK
Kenneth M. Rice
32Cardiovascular Health Research Unit, University of Washington, 1730 Minor Ave. Suite 1360, Seattle, WA 98101, USA
62Department of Biostatistics, University of Washington, Seattle, WA, USA
Neil Robertson
4Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK, OX3 7BN
Serena Sanna
60Italian National Research Council, Institute of Genetics and Biomedic Research, Cittadella Universitaria, Monserrato (CA) 09042, Italy
63University of Groningen, University Medical Center Groningen, Department of Genetics, 9700 RB Groningen, the Netherlands
Yuan Shi
64Singapore Eye Research Institute, Singapore National Eye Centre, The Academia, 20 College Road, Singapore 169856
Albert Vernon Smith
40Icelandic Heart Association, Hotlasmari 1, 201 Kopavogur, Iceland
65Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland
Jennifer A. Smith
31Department of Epidemiology, School of Public Health, University of Michigan, 1415 Washington Hgts, Ann Arbor, MI, 48109, USA
66Survey Research Center, Institute for Social Research, University of Michigan, 426 Thompson St, Ann Arbor, MI 48104
Lorraine Southam
8Department of Human Genetics, Wellcome Sanger Institute, Genome Campus, Hinxton, Cambridge, CB10 1SA, UK
4Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK, OX3 7BN
67Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
Heather M. Stringham
12Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA
Salman M. Tajuddin
68Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
Vinicius Tragante
69Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, 3584CX Utrecht, The Netherlands
Sander W. van der Laan
70Experimental Cardiology Laboratory, Division Heart and Lungs, University Medical Center Utrecht, 3584 CX Utrecht, Utrecht, the Netherlands
71Laboratory of Clinical Chemistry and Hematology, University Medical Center Utrecht, 3584 CX Utrecht, Utrecht, the Netherlands
Helen R. Warren
43William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK
72NIHR Barts Cardiovascular Research Unit, Barts and The London School of Medicine & Dentistry, Queen Mary University, London, London, EC1M 6BQ, UK
Jie Yao
16Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, LABiomed at Harbor-UCLA Medical Center, Torrance, CA, USA
Andrianos M. Yiorkas
73Section of Investigative Medicine, Department of Medicine, Imperial College London, London, W12 0NN, UK
74Department of Life Sciences, Brunel University London, London, UB8 3PH, UK
Weihua Zhang
75Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK
76Ealing Hospital, London North West Healthcare NHS Trust, Middlesex UB1 3HW, UK
Wei Zhao
31Department of Epidemiology, School of Public Health, University of Michigan, 1415 Washington Hgts, Ann Arbor, MI, 48109, USA
Emma Ahlqvist
77Lund University Diabetes Centre, Department of Clinical Sciences Malmö, Lund University, Skåne University Hospital, SE-20502 Malmö, Sweden
Mariaelisa Graff
78Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA
Heather M. Highland
78Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA
79Human 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
78Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA
Ken Sin Lo
80Montreal Heart Institute, Université de Montréal, Montreal, Quebec, H1T 1C8, Canada
Eirini Marouli
43William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK
Carolina Medina-Gomez
38Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 GE, The Netherlands
81Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, 3015 GE, the Netherlands
Saima Afaq
41Department 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
43William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK
82Department of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
Najaf Amin
38Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 GE, The Netherlands
Folkert W. Asselbergs
69Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, 3584CX Utrecht, The Netherlands
83Durrer Center for Cardiovascular Research, Netherlands Heart Institute, 3501DG Utrecht, Netherlands
84Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, WC1E 6BT London, United Kingdom
Lori L. Bonnycastle
85Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA
Michiel L. Bots
86Center for Circulatory Health, University Medical Center Utrecht, 3508GA Utrecht, the Netherlands
Ivan Brandslund
87Department of Clinical Biochemistry, Lillebaelt Hospital Vejle, 7100 Vejle, Denmark
Ji Chen
8Department of Human Genetics, Wellcome Sanger Institute, Genome Campus, Hinxton, Cambridge, CB10 1SA, UK
Cramer Christensen
88Medical Department, Lillebaelt Hospital Vejle, 7100 Vejle, Denmark
John Danesh
89Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB18RN, UK
Renée de Mutsert
17Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, 2333 ZA, the Netherlands
Abbas Dehghan
38Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 GE, The Netherlands
90Department of Biostatistics and Epidemiology, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London
91UK Dementia Research Institute at Imperial College London, London, United Kingdom
Tapani Ebeling
92Oulu University Hospital, 90220 Oulu, Finland
Paul Elliott
41Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of Public Health, Imperial College London, London W2 1PG, United Kingdom
93Imperial College NIHR Biomedical Research Centre, London, United Kingdom
94Health Data Research UK – London at Imperial College London, United Kingdom
Aliki-Eleni Farmaki
95Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, 17671, Greece
96Department of Population Science and Experimental Medicine, Institute of Cardiovascular Science, University College London, London, UK
Jessica D. Faul
66Survey Research Center, Institute for Social Research, University of Michigan, 426 Thompson St, Ann Arbor, MI 48104
Paul W. Franks
19Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, SE-205 02, Sweden
97Department of Nutrition, Harvard School of Public Health, Boston, USA
6Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children’s Hospital, Boston, MA 02115
Steve Franks
98Institute of Reproductive and Developmental Biology, Imperial College London,W12 0NN London, UK
Andreas Fritsche
99Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology, and Clinical Chemistry, University Hospital of Tübingen, Tübingen Germany
56German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany
Anette P. Gjesing
18Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
Mark O. Goodarzi
100Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
Vilmundur Gudnason
40Icelandic Heart Association, Hotlasmari 1, 201 Kopavogur, Iceland
65Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland
Göran Hallmans
101Department of Biobank Research, Umeå University, Umeå, SE-901 87, Sweden
Tamara B. Harris
40Icelandic Heart Association, Hotlasmari 1, 201 Kopavogur, Iceland
Karl-Heinz Herzig
102Institute of Biomedicine and Biocenter of Oulu, Faculty of Medicine, Medical Research Center Oulu and Oulu University Hospital (K.-H.H.), Oulu, Finland
103Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, 60-572 Poznan, Poland
Marie-France Hivert
104Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, MA, USA
105Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA
Jan-Håkan Jansson
106Department of Public Health and Clinical Medicine, Umeå University, Umeå, SE-901 85, Sweden
Min A Jhun
31Department of Epidemiology, School of Public Health, University of Michigan, 1415 Washington Hgts, Ann Arbor, MI, 48109, USA
107Division of Public Health Sciences, Fred Hutchison Cancer Research Center, Seattle, Washington, 98109, USA
Torben Jørgensen
108Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, 2000 Frederiksberg, Denmark
109Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
110Faculty of Medicine, University of Aalborg, 9100 Aalborg, Denmark
Marit E. Jørgensen
26Steno Diabetes Center Copenhagen, 2820 Gentofte, Denmark
111National Institute of Public Health, Southern Denmark University, 5000 Odense, Denmark
Pekka Jousilahti
112Department of Public Health Solutions, National Institute for Health and Welfare, FI-00271 Helsinki, Finland
Eero Kajantie
113PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
112Department of Public Health Solutions, National Institute for Health and Welfare, FI-00271 Helsinki, Finland
114Norwegian University of Science and Technology, Department of Clinical and Molecular Medicine, Trondheim, Norway
115Children’s Hospital, Helsinki University Hospital and University of Helsinki
Maria Karaleftheri
116Echinos Medical Centre, Echinos, Greece
Sharon L.R. Kardia
31Department of Epidemiology, School of Public Health, University of Michigan, 1415 Washington Hgts, Ann Arbor, MI, 48109, USA
Leena Kinnunen
112Department of Public Health Solutions, National Institute for Health and Welfare, FI-00271 Helsinki, Finland
Heikki A. Koistinen
112Department of Public Health Solutions, National Institute for Health and Welfare, FI-00271 Helsinki, Finland
117University of Helsinki and Department of Medicine, Helsinki University Central Hospital, P.O.Box 340, Haartmaninkatu 4, Helsinki, FI-00029, Finland
118Minerva Foundation Institute for Medical Research, Biomedicum 2U Helsinki, Tukholmankatu 8, FI-00290 Helsinki, Finland
Pirjo Komulainen
119Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, 70100 Kuopio, Finland
Peter Kovacs
120Integrated Research and Treatment (IFB) Center AdiposityDiseases, University of Leipzig, Liebigstrasse 19-21, 04103 Leipzig, Germany
121Department of Medicine, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany
Johanna Kuusisto
122Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, 70210 Kuopio, Finland
Markku Laakso
122Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, 70210 Kuopio, Finland
Leslie A. Lange
123Department of Medicine, Division of Bioinformatics and Personalized Medicine, University of Colorado Denver, Aurora, CO, USA
Lenore J. Launer
40Icelandic Heart Association, Hotlasmari 1, 201 Kopavogur, Iceland
112Department of Public Health Solutions, National Institute for Health and Welfare, FI-00271 Helsinki, Finland
Jung-Jin Lee
124Department of Biostatistics and Epidemiology, University of Pennsylvania, USA, 19104
Aaron Leong
125Division of General Internal Medicine, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Boston, MA, USA
Jaana Lindström
112Department of Public Health Solutions, National Institute for Health and Welfare, FI-00271 Helsinki, Finland
Jocelyn E. Manning Fox
126Alberta Diabetes Institute IsletCore, University of Alberta, Edmonton, Canada, T6G 2E1
127Department of Pharmacology, University of Alberta, Edmonton, Canada, T6G 2E1
Satu Männistö
112Department of Public Health Solutions, National Institute for Health and Welfare, FI-00271 Helsinki, Finland
Nisa M Maruthur
128Department of Medicine, Division of General Internal Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland
129Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA
48Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Leena Moilanen
130Kuopio University Hospital, 70210 Kuopio, Finland
Antonella Mulas
60Italian National Research Council, Institute of Genetics and Biomedic Research, Cittadella Universitaria, Monserrato (CA) 09042, Italy
131Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, 07100 Sassari, Italy
Mike A. Nalls
132Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, 20892, USA
133Data Tecnica International, LLC, Glen Echo, Maryland 20812, USA
Matthew Neville
1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LE
James S. Pankow
134Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, 55455, USA
Alison Pattie
37Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ
Eva R.B. Petersen
135Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, 5000 Odense, Denmark
Hannu Puolijoki
136South Ostobothnia Central Hospital, 60220 Seinajoki, Finland
Asif Rasheed
137Center for Non-Communicable Diseases, Karachi, Pakistan
Paul Redmond
37Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ
Frida Renström
19Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, SE-205 02, Sweden
101Department of Biobank Research, Umeå University, Umeå, SE-901 87, Sweden
Michael Roden
138Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
139Division of Endocrinology and Diabetology, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany
56German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany
Danish Saleheen
124Department of Biostatistics and Epidemiology, University of Pennsylvania, USA, 19104
137Center for Non-Communicable Diseases, Karachi, Pakistan
Juha Saltevo
140Central Finland Central Hospital, 40620 Jyvaskyla, Finland
Kai Savonen
119Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, 70100 Kuopio, Finland
141Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, 70029 Kuopio, Finland
Sylvain Sebert
44Faculty of Medicine, Center for Life Course Health Research, University of Oulu, Oulu, Finland
42Biocenter Oulu, University of Oulu, Oulu, Finland
Tea Skaaby
108Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, 2000 Frederiksberg, Denmark
Kerrin S Small
142Department of Twin Research and Genetic Epidemiology, King’s College London, London,, SE1 7EH, UK
Alena Stančáková
122Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, 70210 Kuopio, Finland
Jakob Stokholm
25COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital 2820, University of Copenhagen, Copenhagen, Denmark
Konstantin Strauch
143Institute 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
144Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, Singapore 119228
11Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore 117549, Singapore
145Duke-NUS Medical School, Singapore, 8 College Road, Singapore 169857
Kent D. Taylor
16Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, LABiomed at Harbor-UCLA Medical Center, Torrance, CA, USA
Betina H. Thuesen
108Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, 2000 Frederiksberg, Denmark
Anke Tönjes
121Department of Medicine, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany
Emmanouil Tsafantakis
146Anogia Medical Centre, Anogia, Greece
Tiinamaija Tuomi
147Folkhälsan Research Centre, Helsinki, Finland
148Department of Endocrinology, Helsinki University Central Hospital, Helsinki, Finland
149Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland
Jaakko Tuomilehto
112Department of Public Health Solutions, National Institute for Health and Welfare, FI-00271 Helsinki, Finland
150Department of Public Health, University of Helsinki, Helsinki, Finland
151Department of Neuroscience and Preventive Medicine, Danube-University Krems, 3500 Krems, Austria
152Saudi Diabetes Research Group, King Abdulaziz University, 21589 Jeddah, Saudi Arabia
Matti Uusitupa
153Department of Public Health and Clinical Nutrition, University of Eastern Finland, 70210 Kuopio, Finland
Marja Vääräsmäki
154PEDEGO 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, Finland
155Department of Welfare, Children, Adolescents and Families Unit, National Institute for Health and Welfare, Oulu, Finland
Ilonca Vaartjes
86Center for Circulatory Health, University Medical Center Utrecht, 3508GA Utrecht, the Netherlands
Magdalena Zoledziewska
60Italian National Research Council, Institute of Genetics and Biomedic Research, Cittadella Universitaria, Monserrato (CA) 09042, Italy
Goncalo Abecasis
61Center for Statistical Genetics, University of Michigan, 1415 Washington Heights, 48109 Ann Arbor, MI, USA
Beverley Balkau
156INSERM U1018, Centre de recherche en Épidémiologie et Santé des Populations (CESP), Villejuif, France
Hans Bisgaard
25COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital 2820, University of Copenhagen, Copenhagen, Denmark
Alexandra I. Blakemore
74Department of Life Sciences, Brunel University London, London, UB8 3PH, UK
73Section of Investigative Medicine, Department of Medicine, Imperial College London, London, W12 0NN, UK
Matthias Blüher
120Integrated Research and Treatment (IFB) Center AdiposityDiseases, University of Leipzig, Liebigstrasse 19-21, 04103 Leipzig, Germany
121Department of Medicine, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany
Heiner Boeing
157Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), 14558 Nuthetal, Germany
Eric Boerwinkle
158The Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, 77030, USA
Klaus Bønnelykke
25COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital 2820, University of Copenhagen, Copenhagen, Denmark
Erwin P. Bottinger
50The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY, 10069, USA
Mark J. Caulfield
43William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK
72NIHR Barts Cardiovascular Research Unit, Barts and The London School of Medicine & Dentistry, Queen Mary University, London, London, EC1M 6BQ, UK
John C Chambers
41Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of Public Health, Imperial College London, London W2 1PG, United Kingdom
76Ealing Hospital, London North West Healthcare NHS Trust, Middlesex UB1 3HW, UK
159Imperial College Healthcare NHS Trust, London W12 0HS, UK
Daniel I Chasman
35Division of Preventive Medicine, Brigham and Women’s Hospital, Boston MA, 02215, USA
160Harvard School of Medicine, Boston MA, 02115, USA
161Division of Genetics, Brigham and Women’s Hospital and Harvard Medical School, Boston MA, USA
Ching-Yu Cheng
64Singapore Eye Research Institute, Singapore National Eye Centre, The Academia, 20 College Road, Singapore 169856
162Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, 8 College Road, Singapore 169857
163Department of Ophthalmology, Yong Loo Lin School of Medicine,National University of Singapore, Singapore, 1E Kent Ridge Rd, Singapore 119228
Anne Clark
1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LE
Francis S. Collins
85Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA
Josef Coresh
48Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
129Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA
Francesco Cucca
60Italian National Research Council, Institute of Genetics and Biomedic Research, Cittadella Universitaria, Monserrato (CA) 09042, Italy
131Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, 07100 Sassari, Italy
Gert J. de Borst
164Department of Vascular Surgery; Division of Surgical Specialties; University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands
Ian J. Deary
36Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ
37Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ
George Dedoussis
95Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, 17671, Greece
Panos Deloukas
43William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK
165Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia
Hester M. den Ruijter
70Experimental Cardiology Laboratory, Division Heart and Lungs, University Medical Center Utrecht, 3584 CX Utrecht, Utrecht, the Netherlands
Josée Dupuis
15Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
166National Heart, Lung, and Blood Institute (NHLBI) Framingham Heart Study, Framingham, MA, USA
Michele K. Evans
68Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
Ele Ferrannini
167CNR Institute of Clinical Physiology, Pisa, Italy, Department of Clinical & Experimental Medicine, University of Pisa, Italy
Oscar H Franco
38Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 GE, The Netherlands
59Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland
Harald Grallert
55Institute of Epidemiology II, Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German
56German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany
Leif Groop
168Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Malmö, Sweden
149Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland
Torben Hansen
18Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
169Faculty of Health Sciences, University of Southern Denmark, 5000 Odense, Denmark
Andrew T. Hattersley
170University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK
Caroline Hayward
54Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK
Joel N. Hirschhorn
171Departments of Pediatrics and Genetics, Harvard Medical School, Boston, MA 02115
6Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children’s Hospital, Boston, MA 02115
7Broad Institute of MIT and Harvard, Cambridge, MA, 02142
Arfan Ikram
38Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 GE, The Netherlands
Erik Ingelsson
46Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
39Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, 75237, Sweden
172Stanford Cardiovascular Institute, Stanford University, Stanford, CA 94305
173Stanford Diabetes Research Center, Stanford University, Stanford, CA 94305
Fredrik Karpe
1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LE
174Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK, OX3 7LE
Kay-Tee Kaw
175Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Strangeways Research Laboratory, Cambridge, CB1 8RN, UK
Wieland Kiess
176Pediatric Research Center, Department of Women & Child Health, University of Leipzig, Leipzig, Germany
Jaspal S Kooner
177National Heart and Lung Institute, Imperial College London, London W12 0NN, UK
76Ealing Hospital, London North West Healthcare NHS Trust, Middlesex UB1 3HW, UK
159Imperial College Healthcare NHS Trust, London W12 0HS, UK
Antje Körner
176Pediatric Research Center, Department of Women & Child Health, University of Leipzig, Leipzig, Germany
Timo Lakka
178Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio Campus, 70211 Kuopio, Finland
119Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, 70100 Kuopio, Finland
141Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, 70029 Kuopio, Finland
Claudia Langenberg
3MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
Lars Lind
179Department of Medical Sciences, Molecular Epidemiology; EpiHealth, Uppsala University, Uppsala, 75185, Sweden
Cecilia M Lindgren
4Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK, OX3 7BN
180The Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7BN, UK
Allan Linneberg
108Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, 2000 Frederiksberg, Denmark
181Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
Leonard Lipovich
24Center for Molecular Medicine and Genetics, Wayne State University, 540 E. Canfield St., 3208 Scott Hall, Detroit, Michigan 48201-1928, U.S.A.
182Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA
Ching-Ti Liu
15Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
Jun Liu
38Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 GE, The Netherlands
Yongmei Liu
183Department of Epidemiology & Prevention, Division of Public Health Sciences, Wake Forest University, Winston-Salem, NC, 27157, USA
Ruth J.F. Loos
50The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY, 10069, USA
184The Mindich Child Health and Development Institute, The Icahn School of Medicine at Mount Sinai, New York, NY, 10069, USA
Patrick E. MacDonald
126Alberta Diabetes Institute IsletCore, University of Alberta, Edmonton, Canada, T6G 2E1
127Department of Pharmacology, University of Alberta, Edmonton, Canada, T6G 2E1
Karen L. Mohlke
185Department of Genetics, University of North Carolina, Chapel Hill, NC, 27599, USA
Andrew D Morris
186Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH16 4UX, UK
Patricia B. Munroe
43William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK
72NIHR Barts Cardiovascular Research Unit, Barts and The London School of Medicine & Dentistry, Queen Mary University, London, London, EC1M 6BQ, UK
Alison Murray
187Aberdeen Biomedical Imaging Centre, University of Aberdeen, Foresterhill Health Campus, Aberdeen, AB25 2ZD
Sandosh Padmanabhan
188British 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
189Division of Population Health and Genomics, School of Medicine, University of Dundee, DUNEE DD2 4BF
Gerard Pasterkamp
70Experimental Cardiology Laboratory, Division Heart and Lungs, University Medical Center Utrecht, 3584 CX Utrecht, Utrecht, the Netherlands
71Laboratory of Clinical Chemistry and Hematology, University Medical Center Utrecht, 3584 CX Utrecht, Utrecht, the Netherlands
Oluf Pedersen
18Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
Patricia A. Peyser
31Department of Epidemiology, School of Public Health, University of Michigan, 1415 Washington Hgts, Ann Arbor, MI, 48109, USA
Ozren Polasek
190Faculty of Medicine, University of Split, Split, Croatia
David Porteous
34Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK
Michael A. Province
27Department of Genetics, Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri 63108, USA
Bruce M Psaty
32Cardiovascular Health Research Unit, University of Washington, 1730 Minor Ave. Suite 1360, Seattle, WA 98101, USA
33Department of Medicine, University of Washington, Seattle, WA, USA
191Departments of Epidemiology and Health Services, University of Washington, Seattle, WA, USA
192Kaiser Permanent Washington Health Research Institute, Seattle, WA, USA
Rainer Rauramaa
119Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, 70100 Kuopio, Finland
Paul M Ridker
35Division of Preventive Medicine, Brigham and Women’s Hospital, Boston MA, 02215, USA
160Harvard School of Medicine, Boston MA, 02115, USA
193Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston MA 02115
Olov Rolandsson
194Department of Public Health & Clinical Medicine, Section for Family Medicine, Umeå University, Umeå, SE-901 85, Sweden
Patrik Rorsman
1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LE
174Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK, OX3 7LE
Frits R. Rosendaal
17Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, 2333 ZA, the Netherlands
Igor Rudan
186Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH16 4UX, UK
Veikko Salomaa
112Department of Public Health Solutions, National Institute for Health and Welfare, FI-00271 Helsinki, Finland
Matthias B. Schulze
57Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany
56German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany
Robert Sladek
195Department of Medicine, McGill University, Montreal (Quebec) Canada H4A 3J1
196Department of Human Genetics, McGill University, Montreal (Quebec) Canada H3A 1B1
Blair H Smith
189Division of Population Health and Genomics, School of Medicine, University of Dundee, DUNEE DD2 4BF
Timothy D Spector
142Department of Twin Research and Genetic Epidemiology, King’s College London, London,, SE1 7EH, UK
John M. Starr
197Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, EH8 9JZ
36Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ
Michael Stumvoll
121Department of Medicine, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany
Cornelia M van Duijn
38Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 GE, The Netherlands
Mark Walker
198Institute of Cellular Medicine, The Medical School, Newcastle University, Newcastle, NE2 4HH, UK
Nick J. Wareham
3MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
David R. Weir
66Survey Research Center, Institute for Social Research, University of Michigan, 426 Thompson St, Ann Arbor, MI 48104
James G. Wilson
199Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA
Tien Yin Wong
64Singapore Eye Research Institute, Singapore National Eye Centre, The Academia, 20 College Road, Singapore 169856
162Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, 8 College Road, Singapore 169857
163Department of Ophthalmology, Yong Loo Lin School of Medicine,National University of Singapore, Singapore, 1E Kent Ridge Rd, Singapore 119228
Eleftheria Zeggini
8Department of Human Genetics, Wellcome Sanger Institute, Genome Campus, Hinxton, Cambridge, CB10 1SA, UK
67Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
Alan B. Zonderman
68Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
Jerome I. Rotter
16Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, LABiomed at Harbor-UCLA Medical Center, Torrance, CA, USA
Andrew P. Morris
200Department of Biostatistics, University of Liverpool, Liverpool L69 3GL, UK
4Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK, OX3 7BN
Michael Boehnke
12Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA
Jose Florez
201Diabetes Unit, Department of Medicine, Massachusetts General, Boston, MA, USA
202Program in Medical Genetics, Broad Institute, Cambridge, MA, USA
Mark I McCarthy
4Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK, OX3 7BN
1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LE
174Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK, OX3 7LE
James B Meigs
125Division of General Internal Medicine, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Boston, MA, USA
202Program in Medical Genetics, Broad Institute, Cambridge, MA, USA
Anubha Mahajan
4Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK, OX3 7BN
Robert A. Scott
3MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
Anna L Gloyn
1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK, OX3 7LE
4Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK, OX3 7BN
174Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK, OX3 7LE
Inês Barroso
8Department of Human Genetics, Wellcome Sanger Institute, Genome Campus, Hinxton, Cambridge, CB10 1SA, UK
3MRC 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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