Large-scale exome array summary statistics resources for glycemic traits to aid effector gene prioritization

Sara M Willems^#^{1

2}, Natasha H J Ng^#^{3

4}, Juan Fernandez⁵, Rebecca S Fine^{6

7

8

9}, Eleanor Wheeler^{1

10}, Jennifer Wessel^{8

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13}, Hidetoshi Kitajima⁵, Gaelle Marenne¹⁰, Xueling Sim^{14

15}, Hanieh Yaghootkar¹⁶, Shuai Wang¹⁷, Sai Chen¹⁵, Yuning Chen¹⁷, Yii-Der Ida Chen¹⁸, Niels Grarup¹⁹, Ruifang Li-Gao²⁰, Tibor V Varga²¹, Jennifer L Asimit^{10

22}, Shuang Feng²³, Rona J Strawbridge^{24

25}, Erica L Kleinbrink^{26

27}, Tarunveer S Ahluwalia^{28

29}, Ping An³⁰, Emil V Appel¹⁹, Dan E Arking³¹, Juha Auvinen^{32

33}, Lawrence F Bielak³⁴, Nathan A Bihlmeyer³⁵, Jette Bork-Jensen¹⁹, Jennifer A Brody^{36

37}, Archie Campbell³⁸, Audrey Y Chu³⁹, Gail Davies^{40

41}, Ayse Demirkan⁴², James S Floyd^{36

37}, Franco Giulianini³⁹, Xiuqing Guo¹⁸, Stefan Gustafsson⁴³, Anne U Jackson¹⁵, Johanna Jakobsdottir⁴⁴, Marjo-Riitta Järvelin^{32

45

46}, Richard A Jensen^{36

37}, Stavroula Kanoni⁴⁷, Sirkka Keinanen-Kiukaanniemi^{48

49}, Man Li^{50

51}, Yingchang Lu^{52

53}, Jian'an Luan¹, Alisa K Manning^{54

55}, Jonathan Marten⁵⁶, Karina Meidtner^{57

58}, Dennis O Mook-Kanamori^{20

59}, Taulant Muka^{42

60}, Giorgio Pistis^{61

62}, Bram Prins¹⁰, Kenneth M Rice^{36

63}, Serena Sanna^{61

64}, Albert Vernon Smith^{44

65}, Jennifer A Smith^{34

66}, Lorraine Southam^{5

10

67}, Heather M Stringham¹⁵, Vinicius Tragante⁶⁸, Sander W van der Laan⁶⁹, Helen R Warren^{47

70}, Jie Yao¹⁸, Andrianos M Yiorkas^{71

72}, Weihua Zhang^{73

74}, Wei Zhao³⁴, Mariaelisa Graff⁷⁵, Heather M Highland^{75

76}, Anne E Justice⁷⁵, Eirini Marouli⁴⁷, Carolina Medina-Gomez^{42

77}, Saima Afaq⁴⁵, Wesam A Alhejily^{47

78}, Najaf Amin⁴², Folkert W Asselbergs^{79

80}, Lori L Bonnycastle⁸¹, Michiel L Bots⁸², Ivan Brandslund^{83

84}, Ji Chen¹⁰, John Danesh⁸⁵, Renée de Mutsert²⁰, Abbas Dehghan^{42

45

86}, Tapani Ebeling⁸⁷, Paul Elliott^{45

88

89}; EPIC-Interact Consortium; Aliki-Eleni Farmaki^{90

91}, Jessica D Faul⁶⁶, Paul W Franks^{7

21

92}, Steve Franks⁹³, Andreas Fritsche^{58

94}, Anette P Gjesing¹⁹, Mark O Goodarzi⁹⁵, Vilmundur Gudnason^{44

65}, Göran Hallmans⁹⁶, Tamara B Harris⁴⁴, Karl-Heinz Herzig^{97

98}, Marie-France Hivert^{99

100}, Torben Jørgensen^{101

102

103}, Marit E Jørgensen^{29

104}, Pekka Jousilahti¹⁰⁵, Eero Kajantie^{105

106

107

108}, Maria Karaleftheri¹⁰⁹, Sharon L R Kardia³⁴, Leena Kinnunen¹⁰⁵, Heikki A Koistinen^{105

110

111}, Pirjo Komulainen¹¹², Peter Kovacs^{113

114}, Johanna Kuusisto¹¹⁵, Markku Laakso¹¹⁵, Leslie A Lange¹¹⁶, Lenore J Launer¹¹⁷, Aaron Leong¹¹⁸, Jaana Lindström¹⁰⁵, Jocelyn E Manning Fox^{119

120}, Satu Männistö¹⁰⁵, Nisa M Maruthur^{51

121

122}, Leena Moilanen¹²³, Antonella Mulas^{61

124}, Mike A Nalls^{125

126}, Matthew Neville³, James S Pankow¹²⁷, Alison Pattie⁴¹, Eva R B Petersen⁸³, Hannu Puolijoki¹²⁸, Asif Rasheed¹²⁹, Paul Redmond⁴¹, Frida Renström^{21

96}, Michael Roden^{58

130

131}, Danish Saleheen^{129

132}, Juha Saltevo¹³³, Kai Savonen^{112

134}, Sylvain Sebert^{46

48}, Tea Skaaby¹⁰¹, Kerrin S Small¹³⁵, Alena Stančáková¹¹⁵, Jakob Stokholm²⁸, Konstantin Strauch¹³⁶, E-Shyong Tai^{14

137

138}, Kent D Taylor¹⁸, Betina H Thuesen¹⁰¹, Anke Tönjes¹³⁹, Emmanouil Tsafantakis¹⁴⁰, Tiinamaija Tuomi^{141

142

143

144}, Jaakko Tuomilehto^{105

145

146}; Understanding Society Scientific Group; Matti Uusitupa¹⁴⁷, Marja Vääräsmäki^{106

148}, Ilonca Vaartjes⁸², Magdalena Zoledziewska⁶¹, Goncalo Abecasis⁶², Beverley Balkau¹⁴⁹, Hans Bisgaard²⁸, Alexandra I Blakemore^{71

72}, Matthias Blüher^{139

150}, Heiner Boeing¹⁵¹, Eric Boerwinkle¹⁵², Klaus Bønnelykke²⁸, Erwin P Bottinger⁵², Mark J Caulfield^{47

70}, John C Chambers^{45

74

153}, Daniel I Chasman^{39

154

155}, Ching-Yu Cheng^{156

157

158}, Francis S Collins⁸¹, Josef Coresh^{51

122}, Francesco Cucca^{61

124}, Gert J de Borst¹⁵⁹, Ian J Deary^{40

41}, George Dedoussis⁹⁰, Panos Deloukas^{47

160}, Hester M den Ruijter¹⁶¹, Josée Dupuis^{17

162}, Michele K Evans¹¹⁷, Ele Ferrannini¹⁶³, Oscar H Franco^{42

60}, Harald Grallert^{58

164}, Torben Hansen^{19

165}, Andrew T Hattersley¹⁶⁶, Caroline Hayward⁵⁶, Joel N Hirschhorn^{7

8

167}, Arfan Ikram⁴², Erik Ingelsson^{168

169

170}, Fredrik Karpe^{3

171}, Kay-Tee Kaw¹⁷², Wieland Kiess¹⁷³, Jaspal S Kooner^{74

153

174}, Antje Körner¹⁷³, Timo Lakka^{112

134

175}, Claudia Langenberg¹, Lars Lind¹⁷⁶, Cecilia M Lindgren^{5

177}, Allan Linneberg^{101

178}, Leonard Lipovich^{27

179}, Ching-Ti Liu¹⁷, Jun Liu⁴², Yongmei Liu¹⁸⁰, Ruth J F Loos^{52

181}, Patrick E MacDonald^{119

120}, Karen L Mohlke¹⁸², Andrew D Morris¹⁸³, Patricia B Munroe^{47

70}, Alison Murray¹⁸⁴, Sandosh Padmanabhan¹⁸⁵, Colin N A Palmer¹⁸⁶, Gerard Pasterkamp^{161

187}, Oluf Pedersen¹⁹, Patricia A Peyser³⁴, Ozren Polasek¹⁸⁸, David Porteous³⁸, Michael A Province³⁰, Bruce M Psaty^{36

37

189}, Rainer Rauramaa¹¹², Paul M Ridker^{39

154

190}, Olov Rolandsson¹⁹¹, Patrik Rorsman^{3

171}, Frits R Rosendaal²⁰, Igor Rudan¹⁸³, Veikko Salomaa¹⁰⁵, Matthias B Schulze^{57

58}, Robert Sladek^{192

193}, Blair H Smith¹⁸⁶, Timothy D Spector¹³⁵, John M Starr^{40

194}, Michael Stumvoll¹³⁹, Cornelia M van Duijn⁴², Mark Walker¹⁹⁵, Nick J Wareham¹, David R Weir⁶⁶, James G Wilson¹⁹⁶, Tien Yin Wong^{156

157

158}, Eleftheria Zeggini^{10

67

197}, Alan B Zonderman¹¹⁷, Jerome I Rotter¹⁸, Andrew P Morris¹⁹⁸, Michael Boehnke¹⁵, Jose C Florez^{55

199

200}, Mark I McCarthy^{3

5

171

201}, James B Meigs^{118

200}, Anubha Mahajan^{5

201}, Robert A Scott¹, Anna L Gloyn^{3

5

171

202}, Inês Barroso^{1

10

203}

Affiliations

¹ MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
² General Medicine Center, Saarland University Faculty of Medicine, Homburg, 66421, Germany.
³ Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, OX3 7LE, UK.
⁴ Stem Cells and Diabetes Laboratory, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore, 138673, Singapore.
⁵ Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
⁶ Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA.
⁷ Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, MA, 02115, USA.
⁸ Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
⁹ Current address: Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA, 02210, USA.
¹⁰ Department of Human Genetics, Wellcome Sanger Institute, Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
¹¹ Departments of Epidemiology & Medicine, Schools of Public Health & Medicine, Indiana University, Indianapolis, IN, 46202, USA.
¹² Diabetes Translational Research Center, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
¹³ General Medicine Division, Massachusetts General Hospital, Boston, MA, USA.
¹⁴ Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore, 117549, Singapore.
¹⁵ Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, 48109, USA.
¹⁶ Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
¹⁷ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
¹⁸ The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
¹⁹ Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2200, Denmark.
²⁰ Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands.
²¹ Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, SE-205 02, Sweden.
²² MRC Biostatistics Unit, University of Cambridge, Cambridge, CB2 0SR, UK.
²³ Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
²⁴ Mental Health and Wellbeing, School of Health and Wellbeing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8RZ, UK.
²⁵ Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institute, Stockholm, 171 76, Sweden.
²⁶ Quantitative Life Sciences, McGill University, Montreal, Quebec, Canada.
²⁷ Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, 48201-1928, USA.
²⁸ COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
²⁹ Steno Diabetes Center Copenhagen, Gentofte, 2820, Denmark.
³⁰ Department of Genetics, Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri, 63108, USA.
³¹ McKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³² Center for Life Course Health Research, University of Oulu, Oulu, 90014, Finland.
³³ Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
³⁴ Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA.
³⁵ McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³⁶ Cardiovascular Health Research Unit, University of Washington, Seattle, WA, 98195, USA.
³⁷ Department of Medicine, University of Washington, Seattle, WA, USA.
³⁸ Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.
³⁹ Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, 02215, USA.
⁴⁰ Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
⁴¹ Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
⁴² Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 GE, The Netherlands.
⁴³ Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, 75237, Sweden.
⁴⁴ Icelandic Heart Association, Kopavogur, Iceland.
⁴⁵ Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of Public Health, Imperial College London, London, W2 1PG, UK.
⁴⁶ Biocenter Oulu, University of Oulu, Oulu, Finland.
⁴⁷ William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
⁴⁸ Faculty of Medicine, Center for Life Course Health Research, University of Oulu, Oulu, Finland.
⁴⁹ MRC and Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
⁵⁰ Division of Nephrology, Internal Medicine, School of Medicine, University of Utah, Salt Lake City, USA.
⁵¹ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
⁵² The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY, 10069, USA.
⁵³ Department of Medicine, Division of Genetic Medicine, Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, TN, 37203, USA.
⁵⁴ Center for Human Genetics Research, Massachusetts General Hospital, Boston, MA, 02114, USA.
⁵⁵ Department of Medicine, Harvard Medical School, Boston, MA, USA.
⁵⁶ Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.
⁵⁷ Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, 14558, Germany.
⁵⁸ German Center for Diabetes Research (DZD), München-Neuherberg, 85764, Germany.
⁵⁹ Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands.
⁶⁰ Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
⁶¹ Italian National Research Council, Institute of Genetics and Biomedic Research, Cittadella Universitaria, Monserrato, 09042, Italy.
⁶² Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, 48109, USA.
⁶³ Department of Biostatistics, University of Washington, Seattle, WA, USA.
⁶⁴ University Medical Center Groningen, Department of Genetics, University of Groningen, Groningen, 9700 RB, The Netherlands.
⁶⁵ Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
⁶⁶ Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, 48104, USA.
⁶⁷ Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
⁶⁸ Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, 3584CX, The Netherlands.
⁶⁹ Central Diagnostics Laboratory, Division Laboratories, Pharmacy, and Biomedical genetics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
⁷⁰ Barts Cardiovascular Research Unit, Barts and The London School of Medicine & Dentistry, Queen Mary University, London, EC1M 6BQ, UK.
⁷¹ Section of Investigative Medicine, Department of Medicine, Imperial College London, London, W12 0NN, UK.
⁷² Department of Life Sciences, Brunel University London, London, UB8 3PH, UK.
⁷³ Department of Epidemiology and Biostatistics, Imperial College London, London, W2 1PG, UK.
⁷⁴ Ealing Hospital, London North West Healthcare NHS Trust, Middlesex, UB1 3HW, UK.
⁷⁵ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA.
⁷⁶ Human 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.
⁷⁷ Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, 3015 GE, The Netherlands.
⁷⁸ Department of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
⁷⁹ Amsterdam University Medical Centers, Department of Cardiology, University of Amsterdam, Amsterdam, The Netherlands.
⁸⁰ Health Data Research UK and Institute of Health Informatics, University College London, London, UK.
⁸¹ Center for Precision Health Research, National Human Genome Research Institute, NIH, Bethesda, MD, 20892, USA.
⁸² Center for Circulatory Health, University Medical Center Utrecht, Utrecht, 3508GA, The Netherlands.
⁸³ Department of Clinical Biochemistry, Lillebaelt Hospital Vejle, Vejle, 7100, Denmark.
⁸⁴ Institute of Regional Health Research, University of Southern Denmark, Odense, 5000, Denmark.
⁸⁵ Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB18RN, UK.
⁸⁶ UK Dementia Research Institute, Imperial College London, London, UK.
⁸⁷ Oulu University Hospital, Oulu, 90220, Finland.
⁸⁸ Imperial College NIHR Biomedical Research Centre, London, UK.
⁸⁹ Health Data Research UK, Imperial College London, London, UK.
⁹⁰ Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, 17671, Greece.
⁹¹ Department of Population Science and Experimental Medicine, Institute of Cardiovascular Science, University College London, London, UK.
⁹² Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
⁹³ Institute of Reproductive and Developmental Biology, Imperial College London, London, W12 0NN, UK.
⁹⁴ Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology, and Clinical Chemistry, University Hospital of Tübingen, Tübingen, Germany.
⁹⁵ Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
⁹⁶ Department of Biobank Research, Umeå University, Umeå, SE-901 87, Sweden.
⁹⁷ Institute of Biomedicine and Biocenter of Oulu, Faculty of Medicine, Medical Research Center Oulu and Oulu University Hospital, Oulu, Finland.
⁹⁸ Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, Poznan, 60-572, Poland.
⁹⁹ Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, MA, USA.
¹⁰⁰ Diabetes Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
¹⁰¹ Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Frederiksberg, 2000, Denmark.
¹⁰² Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2200, Denmark.
¹⁰³ Faculty of Medicine, University of Aalborg, Aalborg, 9100, Denmark.
¹⁰⁴ National Institute of Public Health, Southern Denmark University, Odense, 5000, Denmark.
¹⁰⁵ Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, FI-00271, Finland.
¹⁰⁶ PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
¹⁰⁷ Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
¹⁰⁸ Children's Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
¹⁰⁹ Echinos Medical Centre, Echinos, Greece.
¹¹⁰ University of Helsinki and Department of Medicine, Helsinki University Hospital, Helsinki, FI-00029, Finland.
¹¹¹ Minerva Foundation Institute for Medical Research, Biomedicum 2U Helsinki, Helsinki, FI-00290, Finland.
¹¹² Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, 70100, Finland.
¹¹³ Integrated Research and Treatment (IFB) Center Adiposity Diseases, University of Leipzig, Leipzig, 04103, Germany.
¹¹⁴ Medical Department III - Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, 04103, Germany.
¹¹⁵ Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, 70210, Finland.
¹¹⁶ Department of Medicine, Division of Bioinformatics and Personalized Medicine, University of Colorado Denver, Denver, CO, USA.
¹¹⁷ Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.
¹¹⁸ Division of General Internal Medicine, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Boston, MA, USA.
¹¹⁹ Alberta Diabetes Institute IsletCore, University of Alberta, Edmonton, T6G 2E1, Canada.
¹²⁰ Department of Pharmacology, University of Alberta, Edmonton, T6G 2E1, Canada.
¹²¹ Department of Medicine, Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹²² Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA.
¹²³ Kuopio University Hospital, Kuopio, 70210, Finland.
¹²⁴ Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, Sassari, 07100, Italy.
¹²⁵ Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, 20892, USA.
¹²⁶ Data Tecnica International LLC, Glen Echo, MD, 20812, USA.
¹²⁷ Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, 55455, USA.
¹²⁸ South Ostobothnia Central Hospital, Seinajoki, 60220, Finland.
¹²⁹ Center for Non-Communicable Diseases, Karachi, Pakistan.
¹³⁰ Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
¹³¹ Division of Endocrinology and Diabetology, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany.
¹³² Department of Biostatistics and Epidemiology, University of Pennsylvania, 19104, USA.
¹³³ Central Finland Central Hospital, Jyvaskyla, 40620, Finland.
¹³⁴ Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, 70029, Finland.
¹³⁵ Department of Twin Research and Genetic Epidemiology, King's College London, London, SE1 7EH, UK.
¹³⁶ Institute of Genetic Epidemiology, Helmholtz Center Munich, German Research Center for Environmental Health, German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
¹³⁷ Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore.
¹³⁸ Duke-NUS Medical School, Singapore, 169857, Singapore.
¹³⁹ Department of Medicine, University of Leipzig, Leipzig, 04103, Germany.
¹⁴⁰ Anogia Medical Centre, Anogia, Greece.
¹⁴¹ Folkhälsan Research Centre, Helsinki, Finland.
¹⁴² Department of Endocrinology, Helsinki University Central Hospital, Helsinki, Finland.
¹⁴³ Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.
¹⁴⁴ Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Malmö, Sweden.
¹⁴⁵ Department of Public Health, University of Helsinki, Helsinki, Finland.
¹⁴⁶ Saudi Diabetes Research Group, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
¹⁴⁷ Department of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, 70210, Finland.
¹⁴⁸ Department of Welfare, Children, Adolescents and Families Unit, National Institute for Health and Welfare, Oulu, Finland.
¹⁴⁹ INSERM U1018, Centre de recherche en Épidémiologie et Santé des Populations (CESP), Villejuif, France.
¹⁵⁰ Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG), Helmholtz Zentrum München, University of Leipzig and University Hospital Leipzig, Leipzig, Germany.
¹⁵¹ Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Nuthetal, 14558, Germany.
¹⁵² The Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, 77030, USA.
¹⁵³ Imperial College Healthcare NHS Trust, London, W12 0HS, UK.
¹⁵⁴ Harvard School of Medicine, Boston, MA, USA.
¹⁵⁵ Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹⁵⁶ Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, 169856, Singapore.
¹⁵⁷ Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, 169857, Singapore.
¹⁵⁸ Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore.
¹⁵⁹ Department of Vascular Surgery, Division of Surgical Specialties, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands.
¹⁶⁰ Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia.
¹⁶¹ Experimental Cardiology Laboratory, Division Heart and Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, 3584 CX, The Netherlands.
¹⁶² Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada.
¹⁶³ CNR Institute of Clinical Physiology, Department of Clinical & Experimental Medicine, University of Pisa, Pisa, Italy.
¹⁶⁴ Institute of Epidemiology II, Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Munich, Germany.
¹⁶⁵ Faculty of Health Sciences, University of Southern Denmark, Odense, 5000, Denmark.
¹⁶⁶ University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
¹⁶⁷ Departments of Pediatrics and Genetics, Harvard Medical School, Boston, MA, 02115, USA.
¹⁶⁸ Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.
¹⁶⁹ Stanford Cardiovascular Institute, Stanford University, Stanford, CA, 94305, USA.
¹⁷⁰ Stanford Diabetes Research Center, Stanford University, Stanford, 94305, USA.
¹⁷¹ Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, OX3 7LE, UK.
¹⁷² Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, CB1 8RN, UK.
¹⁷³ Pediatric Research Center, Department of Women & Child Health, University of Leipzig, Leipzig, Germany.
¹⁷⁴ National Heart and Lung Institute, Imperial College London, London, W12 0NN, UK.
¹⁷⁵ Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio, 70211, Finland.
¹⁷⁶ Department of Medical Sciences, Molecular Epidemiology; EpiHealth, Uppsala University, Uppsala, 75185, Sweden.
¹⁷⁷ The Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, OX3 7BN, UK.
¹⁷⁸ Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2200, Denmark.
¹⁷⁹ Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA.
¹⁸⁰ Department of Epidemiology & Prevention, Division of Public Health Sciences, Wake Forest University, Winston-Salem, NC, 27157, USA.
¹⁸¹ The Mindich Child Health and Development Institute, The Icahn School of Medicine at Mount Sinai, New York, NY, 10069, USA.
¹⁸² Department of Genetics, University of North Carolina, Chapel Hill, NC, 27599, USA.
¹⁸³ Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH16 4UX, UK.
¹⁸⁴ Aberdeen Biomedical Imaging Centre, University of Aberdeen, Foresterhill Health Campus, Aberdeen, AB25 2ZD, UK.
¹⁸⁵ 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.
¹⁸⁶ Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, DD2 4BF, UK.
¹⁸⁷ Laboratory of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands.
¹⁸⁸ Faculty of Medicine, University of Split, Split, Croatia.
¹⁸⁹ Departments of Epidemiology, Health Systems and Population Health, University of Washington, Seattle, Seattle, WA, USA.
¹⁹⁰ Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA.
¹⁹¹ Department of Public Health & Clinical Medicine, Section for Family Medicine, Umeå University, Umeå, SE-901 85, Sweden.
¹⁹² Department of Medicine, McGill University, Montreal, Quebec, H4A 3J1, Canada.
¹⁹³ Department of Human Genetics, McGill University, Montreal, Quebec, H3A 1B1, Canada.
¹⁹⁴ Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
¹⁹⁵ Institute of Cellular Medicine, The Medical School, Newcastle University, Newcastle, NE2 4HH, UK.
¹⁹⁶ Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA.
¹⁹⁷ Technical University of Munich (TUM) and Klinikum Rechts der Isar, TUM School of Medicine, Munich, Germany.
¹⁹⁸ Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, University of Manchester, Manchester, UK.
¹⁹⁹ Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
²⁰⁰ Programs in Metabolism and Medical & Population Genetics, Broad Institute, Cambridge, MA, USA.
²⁰¹ Current address: Genentech, South San Francisco, CA, 94080, USA.
²⁰² Division of Endocrinology, Department of Pediatrics, Stanford School of Medicine, Stanford, CA, USA.
²⁰³ Exeter Centre of Excellence in Diabetes (EXCEED), University of Exeter Medical School, Exeter, UK.

^# Contributed equally.

PMID: 39280063
PMCID: PMC11399760
DOI: 10.12688/wellcomeopenres.18754.1

Large-scale exome array summary statistics resources for glycemic traits to aid effector gene prioritization

Sara M Willems et al. Wellcome Open Res. 2023.

. 2023 Oct 20:8:483.

doi: 10.12688/wellcomeopenres.18754.1. eCollection 2023.

Authors

Affiliations

¹ MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
² General Medicine Center, Saarland University Faculty of Medicine, Homburg, 66421, Germany.
³ Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, OX3 7LE, UK.
⁴ Stem Cells and Diabetes Laboratory, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore, 138673, Singapore.
⁵ Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
⁶ Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA.
⁷ Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, MA, 02115, USA.
⁸ Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
⁹ Current address: Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA, 02210, USA.
¹⁰ Department of Human Genetics, Wellcome Sanger Institute, Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
¹¹ Departments of Epidemiology & Medicine, Schools of Public Health & Medicine, Indiana University, Indianapolis, IN, 46202, USA.
¹² Diabetes Translational Research Center, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
¹³ General Medicine Division, Massachusetts General Hospital, Boston, MA, USA.
¹⁴ Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore, 117549, Singapore.
¹⁵ Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, 48109, USA.
¹⁶ Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
¹⁷ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
¹⁸ The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
¹⁹ Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2200, Denmark.
²⁰ Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands.
²¹ Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, SE-205 02, Sweden.
²² MRC Biostatistics Unit, University of Cambridge, Cambridge, CB2 0SR, UK.
²³ Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
²⁴ Mental Health and Wellbeing, School of Health and Wellbeing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8RZ, UK.
²⁵ Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institute, Stockholm, 171 76, Sweden.
²⁶ Quantitative Life Sciences, McGill University, Montreal, Quebec, Canada.
²⁷ Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, 48201-1928, USA.
²⁸ COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
²⁹ Steno Diabetes Center Copenhagen, Gentofte, 2820, Denmark.
³⁰ Department of Genetics, Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri, 63108, USA.
³¹ McKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³² Center for Life Course Health Research, University of Oulu, Oulu, 90014, Finland.
³³ Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
³⁴ Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA.
³⁵ McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³⁶ Cardiovascular Health Research Unit, University of Washington, Seattle, WA, 98195, USA.
³⁷ Department of Medicine, University of Washington, Seattle, WA, USA.
³⁸ Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.
³⁹ Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, 02215, USA.
⁴⁰ Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
⁴¹ Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
⁴² Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3015 GE, The Netherlands.
⁴³ Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, 75237, Sweden.
⁴⁴ Icelandic Heart Association, Kopavogur, Iceland.
⁴⁵ Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of Public Health, Imperial College London, London, W2 1PG, UK.
⁴⁶ Biocenter Oulu, University of Oulu, Oulu, Finland.
⁴⁷ William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
⁴⁸ Faculty of Medicine, Center for Life Course Health Research, University of Oulu, Oulu, Finland.
⁴⁹ MRC and Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
⁵⁰ Division of Nephrology, Internal Medicine, School of Medicine, University of Utah, Salt Lake City, USA.
⁵¹ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
⁵² The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY, 10069, USA.
⁵³ Department of Medicine, Division of Genetic Medicine, Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, TN, 37203, USA.
⁵⁴ Center for Human Genetics Research, Massachusetts General Hospital, Boston, MA, 02114, USA.
⁵⁵ Department of Medicine, Harvard Medical School, Boston, MA, USA.
⁵⁶ Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.
⁵⁷ Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, 14558, Germany.
⁵⁸ German Center for Diabetes Research (DZD), München-Neuherberg, 85764, Germany.
⁵⁹ Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands.
⁶⁰ Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
⁶¹ Italian National Research Council, Institute of Genetics and Biomedic Research, Cittadella Universitaria, Monserrato, 09042, Italy.
⁶² Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, 48109, USA.
⁶³ Department of Biostatistics, University of Washington, Seattle, WA, USA.
⁶⁴ University Medical Center Groningen, Department of Genetics, University of Groningen, Groningen, 9700 RB, The Netherlands.
⁶⁵ Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
⁶⁶ Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, 48104, USA.
⁶⁷ Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
⁶⁸ Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, 3584CX, The Netherlands.
⁶⁹ Central Diagnostics Laboratory, Division Laboratories, Pharmacy, and Biomedical genetics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
⁷⁰ Barts Cardiovascular Research Unit, Barts and The London School of Medicine & Dentistry, Queen Mary University, London, EC1M 6BQ, UK.
⁷¹ Section of Investigative Medicine, Department of Medicine, Imperial College London, London, W12 0NN, UK.
⁷² Department of Life Sciences, Brunel University London, London, UB8 3PH, UK.
⁷³ Department of Epidemiology and Biostatistics, Imperial College London, London, W2 1PG, UK.
⁷⁴ Ealing Hospital, London North West Healthcare NHS Trust, Middlesex, UB1 3HW, UK.
⁷⁵ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA.
⁷⁶ Human 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.
⁷⁷ Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, 3015 GE, The Netherlands.
⁷⁸ Department of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
⁷⁹ Amsterdam University Medical Centers, Department of Cardiology, University of Amsterdam, Amsterdam, The Netherlands.
⁸⁰ Health Data Research UK and Institute of Health Informatics, University College London, London, UK.
⁸¹ Center for Precision Health Research, National Human Genome Research Institute, NIH, Bethesda, MD, 20892, USA.
⁸² Center for Circulatory Health, University Medical Center Utrecht, Utrecht, 3508GA, The Netherlands.
⁸³ Department of Clinical Biochemistry, Lillebaelt Hospital Vejle, Vejle, 7100, Denmark.
⁸⁴ Institute of Regional Health Research, University of Southern Denmark, Odense, 5000, Denmark.
⁸⁵ Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB18RN, UK.
⁸⁶ UK Dementia Research Institute, Imperial College London, London, UK.
⁸⁷ Oulu University Hospital, Oulu, 90220, Finland.
⁸⁸ Imperial College NIHR Biomedical Research Centre, London, UK.
⁸⁹ Health Data Research UK, Imperial College London, London, UK.
⁹⁰ Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, 17671, Greece.
⁹¹ Department of Population Science and Experimental Medicine, Institute of Cardiovascular Science, University College London, London, UK.
⁹² Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
⁹³ Institute of Reproductive and Developmental Biology, Imperial College London, London, W12 0NN, UK.
⁹⁴ Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology, and Clinical Chemistry, University Hospital of Tübingen, Tübingen, Germany.
⁹⁵ Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
⁹⁶ Department of Biobank Research, Umeå University, Umeå, SE-901 87, Sweden.
⁹⁷ Institute of Biomedicine and Biocenter of Oulu, Faculty of Medicine, Medical Research Center Oulu and Oulu University Hospital, Oulu, Finland.
⁹⁸ Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, Poznan, 60-572, Poland.
⁹⁹ Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, MA, USA.
¹⁰⁰ Diabetes Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
¹⁰¹ Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Frederiksberg, 2000, Denmark.
¹⁰² Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2200, Denmark.
¹⁰³ Faculty of Medicine, University of Aalborg, Aalborg, 9100, Denmark.
¹⁰⁴ National Institute of Public Health, Southern Denmark University, Odense, 5000, Denmark.
¹⁰⁵ Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, FI-00271, Finland.
¹⁰⁶ PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
¹⁰⁷ Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
¹⁰⁸ Children's Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
¹⁰⁹ Echinos Medical Centre, Echinos, Greece.
¹¹⁰ University of Helsinki and Department of Medicine, Helsinki University Hospital, Helsinki, FI-00029, Finland.
¹¹¹ Minerva Foundation Institute for Medical Research, Biomedicum 2U Helsinki, Helsinki, FI-00290, Finland.
¹¹² Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, 70100, Finland.
¹¹³ Integrated Research and Treatment (IFB) Center Adiposity Diseases, University of Leipzig, Leipzig, 04103, Germany.
¹¹⁴ Medical Department III - Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, 04103, Germany.
¹¹⁵ Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, 70210, Finland.
¹¹⁶ Department of Medicine, Division of Bioinformatics and Personalized Medicine, University of Colorado Denver, Denver, CO, USA.
¹¹⁷ Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.
¹¹⁸ Division of General Internal Medicine, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Boston, MA, USA.
¹¹⁹ Alberta Diabetes Institute IsletCore, University of Alberta, Edmonton, T6G 2E1, Canada.
¹²⁰ Department of Pharmacology, University of Alberta, Edmonton, T6G 2E1, Canada.
¹²¹ Department of Medicine, Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹²² Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA.
¹²³ Kuopio University Hospital, Kuopio, 70210, Finland.
¹²⁴ Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, Sassari, 07100, Italy.
¹²⁵ Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, 20892, USA.
¹²⁶ Data Tecnica International LLC, Glen Echo, MD, 20812, USA.
¹²⁷ Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, 55455, USA.
¹²⁸ South Ostobothnia Central Hospital, Seinajoki, 60220, Finland.
¹²⁹ Center for Non-Communicable Diseases, Karachi, Pakistan.
¹³⁰ Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
¹³¹ Division of Endocrinology and Diabetology, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany.
¹³² Department of Biostatistics and Epidemiology, University of Pennsylvania, 19104, USA.
¹³³ Central Finland Central Hospital, Jyvaskyla, 40620, Finland.
¹³⁴ Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, 70029, Finland.
¹³⁵ Department of Twin Research and Genetic Epidemiology, King's College London, London, SE1 7EH, UK.
¹³⁶ Institute of Genetic Epidemiology, Helmholtz Center Munich, German Research Center for Environmental Health, German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
¹³⁷ Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore.
¹³⁸ Duke-NUS Medical School, Singapore, 169857, Singapore.
¹³⁹ Department of Medicine, University of Leipzig, Leipzig, 04103, Germany.
¹⁴⁰ Anogia Medical Centre, Anogia, Greece.
¹⁴¹ Folkhälsan Research Centre, Helsinki, Finland.
¹⁴² Department of Endocrinology, Helsinki University Central Hospital, Helsinki, Finland.
¹⁴³ Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.
¹⁴⁴ Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Malmö, Sweden.
¹⁴⁵ Department of Public Health, University of Helsinki, Helsinki, Finland.
¹⁴⁶ Saudi Diabetes Research Group, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
¹⁴⁷ Department of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, 70210, Finland.
¹⁴⁸ Department of Welfare, Children, Adolescents and Families Unit, National Institute for Health and Welfare, Oulu, Finland.
¹⁴⁹ INSERM U1018, Centre de recherche en Épidémiologie et Santé des Populations (CESP), Villejuif, France.
¹⁵⁰ Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG), Helmholtz Zentrum München, University of Leipzig and University Hospital Leipzig, Leipzig, Germany.
¹⁵¹ Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Nuthetal, 14558, Germany.
¹⁵² The Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, 77030, USA.
¹⁵³ Imperial College Healthcare NHS Trust, London, W12 0HS, UK.
¹⁵⁴ Harvard School of Medicine, Boston, MA, USA.
¹⁵⁵ Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹⁵⁶ Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, 169856, Singapore.
¹⁵⁷ Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, 169857, Singapore.
¹⁵⁸ Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore.
¹⁵⁹ Department of Vascular Surgery, Division of Surgical Specialties, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands.
¹⁶⁰ Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia.
¹⁶¹ Experimental Cardiology Laboratory, Division Heart and Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, 3584 CX, The Netherlands.
¹⁶² Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada.
¹⁶³ CNR Institute of Clinical Physiology, Department of Clinical & Experimental Medicine, University of Pisa, Pisa, Italy.
¹⁶⁴ Institute of Epidemiology II, Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Munich, Germany.
¹⁶⁵ Faculty of Health Sciences, University of Southern Denmark, Odense, 5000, Denmark.
¹⁶⁶ University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
¹⁶⁷ Departments of Pediatrics and Genetics, Harvard Medical School, Boston, MA, 02115, USA.
¹⁶⁸ Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.
¹⁶⁹ Stanford Cardiovascular Institute, Stanford University, Stanford, CA, 94305, USA.
¹⁷⁰ Stanford Diabetes Research Center, Stanford University, Stanford, 94305, USA.
¹⁷¹ Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, OX3 7LE, UK.
¹⁷² Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, CB1 8RN, UK.
¹⁷³ Pediatric Research Center, Department of Women & Child Health, University of Leipzig, Leipzig, Germany.
¹⁷⁴ National Heart and Lung Institute, Imperial College London, London, W12 0NN, UK.
¹⁷⁵ Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio, 70211, Finland.
¹⁷⁶ Department of Medical Sciences, Molecular Epidemiology; EpiHealth, Uppsala University, Uppsala, 75185, Sweden.
¹⁷⁷ The Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, OX3 7BN, UK.
¹⁷⁸ Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2200, Denmark.
¹⁷⁹ Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA.
¹⁸⁰ Department of Epidemiology & Prevention, Division of Public Health Sciences, Wake Forest University, Winston-Salem, NC, 27157, USA.
¹⁸¹ The Mindich Child Health and Development Institute, The Icahn School of Medicine at Mount Sinai, New York, NY, 10069, USA.
¹⁸² Department of Genetics, University of North Carolina, Chapel Hill, NC, 27599, USA.
¹⁸³ Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH16 4UX, UK.
¹⁸⁴ Aberdeen Biomedical Imaging Centre, University of Aberdeen, Foresterhill Health Campus, Aberdeen, AB25 2ZD, UK.
¹⁸⁵ 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.
¹⁸⁶ Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, DD2 4BF, UK.
¹⁸⁷ Laboratory of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands.
¹⁸⁸ Faculty of Medicine, University of Split, Split, Croatia.
¹⁸⁹ Departments of Epidemiology, Health Systems and Population Health, University of Washington, Seattle, Seattle, WA, USA.
¹⁹⁰ Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA.
¹⁹¹ Department of Public Health & Clinical Medicine, Section for Family Medicine, Umeå University, Umeå, SE-901 85, Sweden.
¹⁹² Department of Medicine, McGill University, Montreal, Quebec, H4A 3J1, Canada.
¹⁹³ Department of Human Genetics, McGill University, Montreal, Quebec, H3A 1B1, Canada.
¹⁹⁴ Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
¹⁹⁵ Institute of Cellular Medicine, The Medical School, Newcastle University, Newcastle, NE2 4HH, UK.
¹⁹⁶ Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA.
¹⁹⁷ Technical University of Munich (TUM) and Klinikum Rechts der Isar, TUM School of Medicine, Munich, Germany.
¹⁹⁸ Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, University of Manchester, Manchester, UK.
¹⁹⁹ Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
²⁰⁰ Programs in Metabolism and Medical & Population Genetics, Broad Institute, Cambridge, MA, USA.
²⁰¹ Current address: Genentech, South San Francisco, CA, 94080, USA.
²⁰² Division of Endocrinology, Department of Pediatrics, Stanford School of Medicine, Stanford, CA, USA.
²⁰³ Exeter Centre of Excellence in Diabetes (EXCEED), University of Exeter Medical School, Exeter, UK.

^# Contributed equally.

PMID: 39280063
PMCID: PMC11399760
DOI: 10.12688/wellcomeopenres.18754.1

Abstract

Background: Genome-wide association studies for glycemic traits have identified hundreds of loci associated with these biomarkers of glucose homeostasis. Despite this success, the challenge remains to link variant associations to genes, and underlying biological pathways.

Methods: To identify coding variant associations which may pinpoint effector genes at both novel and previously established genome-wide association loci, we performed meta-analyses of exome-array studies for four glycemic traits: glycated hemoglobin (HbA1c, up to 144,060 participants), fasting glucose (FG, up to 129,665 participants), fasting insulin (FI, up to 104,140) and 2hr glucose post-oral glucose challenge (2hGlu, up to 57,878). In addition, we performed network and pathway analyses.

Results: Single-variant and gene-based association analyses identified coding variant associations at more than 60 genes, which when combined with other datasets may be useful to nominate effector genes. Network and pathway analyses identified pathways related to insulin secretion, zinc transport and fatty acid metabolism. HbA1c associations were strongly enriched in pathways related to blood cell biology.

Conclusions: Our results provided novel glycemic trait associations and highlighted pathways implicated in glycemic regulation. Exome-array summary statistic results are being made available to the scientific community to enable further discoveries.

Keywords: effector genes; exome chip; genetic discovery; glycaemic traits; summary statistics resources.

PubMed Disclaimer

Conflict of interest statement

Competing interests: Rebecca S. Fine: Rebecca S. Fine is currently employed by Vertex Pharmaceuticals Incorporated. Audrey Y Chu: Currently employed by GlaxoSmithkline. Dennis O. Mook-Kanamori: Dennis Mook-Kanamori is working as a part-time clinical research consultant for Metabolon, Inc. Paul W. Franks: PWF has been a paid consultant for Eli Lilly and Sanofi Aventis and has received research support from several pharmaceutical companies as part of a European Union Innovative Medicines Initiative (IMI) project. Mike A. Nalls: Dr. Mike A. Nalls is supported by a consulting contract between Data Tecnica International LLC and the National Institute on Aging (NIA), National Institutes of Health (NIH), Bethesda, MD, USA. Dr. Nalls also consults for Illumina Inc., the Michael J. Fox Foundation, and the University of California Healthcare. Mark J. Caulfield: MJC is Chief Scientist for Genomics England, a UK government company. Joel N. Hirschhorn: JHN is on the scientific advisory board of Camp4 Therapeutics. Erik Ingelsson: Erik Ingelsson is now an employee of GlaxoSmithKline. Anubha Mahajan: Anubha Mahajan is an employee of Genentech since January 2020, and a holder of Roche stock. Mark I McCarthy: The views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. MMcC has served on advisory panels for Pfizer, NovoNordisk and Zoe Global, has received honoraria from Merck, Pfizer, Novo Nordisk and Eli Lilly, and research funding from Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Roche, Sanofi Aventis, Servier, and Takeda. As of June 2019, MMcC is an employee of Genentech, and a holder of Roche stock. Inês Barroso: IB and spouse declare stock ownership in GlaxoSmithkline and Incyte Ltd. James B. Meigs: JBM serves as an Academic Associate for Quest Diagnostics R&D Bruce M Psaty serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Dr. Sander W. van der Laan has received Roche funding for unrelated work. Matthias Blüher received honoraria as a consultant and speaker from Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Lilly, Novo Nordisk, Novartis, Pfizer and Sanofi. Vinicius Tragante: VT became an employee of deCODE genetics/Amgen Inc. after the conclusion of this work Dr Franco is employed by ErasmusAGE, a center for aging research across the life course funded by Nestlé Nutrition (Nestec Ltd.) and Metagenics.

Figures

**Figure 1.. Network and pathway analyses identify relevant gene sets regulating glycemia using two different methods for variant associations with P <1 × 10 ^-5.**
( **A–B**) The networks represent composite networks for ( A) HbA1c and ( B) FG, from the GeneMANIA analysis using genes with variant associations at P <1 × 10 ^-5 for each trait as input. Nodes outlined in red correspond to genes from the input list. Other nodes correspond to related genes based on 50 default databases. Based on the network, GO terms and Reactome pathways that were significantly enriched are depicted. To summarize these results, the most significant term of all calculated terms within the same group is represented. Barplots with the Bonferroni-adjusted -log10(p-values) of the most significant terms within each group are are shown. Each group was assigned a specific color; if a gene is present in more than one term, it is displayed in more than one color. ( **C–D**) Heatmaps showing EC-DEPICT results from analysis of ( C) all traits except HbA1c and ( D) FG. The columns represent the input genes for the analysis. In ( C), these are genes with variant associations of P <1 × 10 ^-5 for FG, FI, and/or 2hGlu, and in ( D) these are genes with variant associations of P <1 × 10 ^-5 for FG. Rows in the heatmap represent significant meta-gene sets (FDR <0.05). The color of each square indicates DEPICT’s z-score for membership of that gene in that gene set, where dark red means “very likely a member” and dark blue means “very unlikely a member.” The gene set annotations indicate whether that meta-gene set was significant at FDR <0.05 or not significant (n.s.) for each of the other EC-DEPICT analyses. For heatmap intensity and EC-DEPICT P-values, the meta-gene set values are taken from the most significantly enriched member gene set. The gene variant annotations are as follows: (1) the European minor allele frequency (MAF) of the input variant, where rare is MAF <1%, low-frequency is MAF 1–5%, and common is MAF >5%, 2) whether the gene has an Online Mendelian Inheritance in Man (OMIM) annotation as causal for a diabetes/glycemic-relevant syndrome or blood disorder, 3) to 6) whether each variant was significant ( P <2 × 10 ^-7), suggestively significant ( P <1 × 10 ^-5), or not significant in Europeans for each of the four traits, and 7) whether each variant was included in the analysis or excluded by filters (see Methods). AWS: array-wide significant.

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References

1. Chen J, Spracklen CN, Marenne G, et al. : The trans-ancestral genomic architecture of glycemic traits. Nat Genet. 2021;53(6):840–860. 10.1038/s41588-021-00852-9 - DOI - PMC - PubMed
1. Downie CG, Dimos SF, Bien SA, et al. : Multi-ethnic GWAS and fine-mapping of glycaemic traits identify novel loci in the PAGE Study. Diabetologia. 2022;65(3):477–489. 10.1007/s00125-021-05635-9 - DOI - PMC - PubMed
1. Mahajan A, Spracklen CN, Zhang W, et al. : Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation. Nat Genet. 2022;54(5):560–572. 10.1038/s41588-022-01058-3 - DOI - PMC - PubMed
1. Mahajan A, Sim X, Ng HJ, et al. : Identification and functional characterization of G6PC2 coding variants influencing glycemic traits define an effector transcript at the G6PC2-ABCB11 locus. PLoS Genet. 2015;11(1): e1004876. 10.1371/journal.pgen.1004876 - DOI - PMC - PubMed
1. Wessel J, Chu AY, Willems SM, et al. : Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility. Nat Commun. 2015;6: 5897. 10.1038/ncomms6897 - DOI - PMC - PubMed

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Large-scale exome array summary statistics resources for glycemic traits to aid effector gene prioritization

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Large-scale exome array summary statistics resources for glycemic traits to aid effector gene prioritization

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