University of Oulu

Chen, J., Spracklen, C.N., Marenne, G. et al. The trans-ancestral genomic architecture of glycemic traits. Nat Genet 53, 840–860 (2021). https://doi.org/10.1038/s41588-021-00852-9

The trans-ancestral genomic architecture of glycemic traits

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Author: Chen, Ji1,2; Spracklen, Cassandra N.3,4; Marenne, Gaelle2,5;
Varshney, Arushi6; Corbin, Laura J.7,8; Luan, Jian'an9; Willems, Sara M.9; Wu, Ying3; Zhang, Xiaoshuai9,10; Horikoshi, Momoko11,12,13; Boutin, Thibaud S.14; Magi, Reedik15; Waage, Johannes16; Li-Gao, Ruifang17; Chan, Kei Hang Katie18,19,20; Yao, Jie21; Anasanti, Mila D.22; Chu, Audrey Y.23; Claringbould, Annique24; Heikkinen, Jani22; Hong, Jaeyoung25; Hottenga, Jouke-Jan26,27; Huo, Shaofeng28; Kaakinen, Marika A.22,29; Louie, Tin30; Maerz, Winfried31,32,33; Moreno-Macias, Hortensia34; Ndungu, Anne12; Nelson, Sarah C.30; Nolte, Ilja M.35; North, Kari E.36; Raulerson, Chelsea K.3; Ray, Debashree37; Rohde, Rebecca36; Rybin, Denis25; Schurmann, Claudia38,39; Sim, Xueling40,41,42,43; Southam, Lorraine2,44; Stewart, Isobel D.9; Wang, Carol A.45; Wang, Yujie36; Wu, Peitao25; Zhang, Weihua46,47; Ahluwalia, Tarunveer S.16,48,49; Appel, Emil V. R.50; Bielak, Lawrence F.51; Brody, Jennifer A.52; Burtt, Noel P.53; Cabrera, Claudia P.54,55; Cade, Brian E.56,57; Chai, Jin Fang40,41; Chai, Xiaoran41,58,59; Chang, Li-Ching60; Chen, Chien-Hsiun60; Chen, Brian H.61; Chitrala, Kumaraswamy Naidu62; Chiu, Yen-Feng63; de Haan, Hugoline G.17; Delgado, Graciela E.33; Demirkan, Ayse29,64; Duan, Qing3,65; Engmann, Jorgen66; Fatumo, Segun A.67,68,69,70; Gayan, Javier71; Giulianini, Franco23; Gong, Jung Ho18; Gustafsson, Stefan72; Hai, Yang73; Hartwig, Fernando P.7,74; He, Jing75; Heianza, Yoriko76; Huang, Tao77; Huerta-Chagoya, Alicia78,79; Hwang, Mi Yeong80; Jensen, Richard A.52; Kawaguchi, Takahisa81; Kentistou, Katherine A.82,83; Kim, Young Jin80; Kleber, Marcus E.; Kooner, Ishminder K.47; Lai, Shuiqing18; Lange, Leslie A.84; Langefeld, Carl D.85; Lauzon, Marie21; Li, Man86; Ligthart, Symen64; Liu, Jun64,87; Loh, Marie46,88; Long, Jirong89; Lyssenko, Valeriya90,91; Mangino, Massimo92,93; Marzi, Carola94,95; Montasser, May E.96; Nag, Abhishek12; Nakatochi, Masahiro97; Noce, Damia98; Noordam, Raymond99; Pistis, Giorgio100; Preuss, Michael38,101; Raffield, Laura3; Rasmussen-Torvik, Laura J.102; Rich, Stephen S.103,104; Robertson, Neil R.11,12; Rueedi, Rico105,106; Ryan, Kathleen96; Sanna, Serena24,100; Saxena, Richa107,108,109; Schraut, Katharina E.82,83; Sennblad, Bengt110; Setoh, Kazuya81; Smith, Albert V.111,112; Sparso, Thomas50; Strawbridge, Rona J.113,114; Takeuchi, Fumihiko115; Tan, Jingyi21; Trompet, Stella99,116; van den Akker, Erik117,118,119; van der Most, Peter J.35; Verweij, Niek120,121; Vogel, Mandy122; Wang, Heming56,57; Wang, Chaolong123,124; Wang, Nan125,126; Warren, Helen R.54,55; Wen, Wanqing89; Wilsgaard, Tom127; Wong, Andrew128; Wood, Andrew R.1; Xie, Tian35; Zafarmand, Mohammad Hadi129,130; Zhao, Jing-Hua131; Zhao, Wei51; Amin, Najaf64,87; Arzumanyan, Zorayr21; Astrup, Arne132; Bakker, Stephan J. L.133; Baldassarre, Damiano134,135; Beekman, Marian117; Bergman, Richard N.136; Bertoni, Alain137; Blueher, Matthias138; Bonnycastle, Lori L.139; Bornstein, Stefan R.140; Bowden, Donald W.141; Cai, Qiuyin75; Campbell, Archie142,143; Campbell, Harry82; Chang, Yi Cheng60,144,145; de Geus, Eco J. C.26,27; Dehghan, Abbas64; Du, Shufa146; Eiriksdottir, Gudny112; Farmaki, Aliki Eleni147,148; Franberg, Mattias114; Fuchsberger, Christian98; Gao, Yutang149; Gjesing, Anette P.50; Goel, Anuj12,150; Han, Sohee80; Hartman, Catharina A.151; Herder, Christian152,153,154; Hicks, Andrew A.98; Hsieh, Chang-Hsun155,156; Hsueh, Willa A.157; Ichihara, Sahoko158; Igase, Michiya159; Ikram, M. Arfan64; Johnson, W. Craig30; Jorgensen, Marit E.48,160; Joshi, Peter K.82; Kalyani, Rita R.161; Kandeel, Fouad R.162; Katsuya, Tomohiro163,164; Khor, Chiea Chuen124; Kiess, Wieland122; Kolcic, Ivana165; Kuulasmaa, Teemu166; Kuusisto, Johanna167,168; Lall, Kristi15; Lam, Kelvin21; Lawlor, Deborah A.7,8; Lee, Nanette R.169,170; Lemaitre, Rozenn N.52; Li, Honglan171,172; Lin, Shih-Yi173,174; Lindstrom, Jaana175; Linneberg, Allan176,177; Liu, Jianjun41,124,178; Lorenzo, Carlos179; Matsubara, Tatsuaki180; Matsuda, Fumihiko81; Mingrone, Geltrude181; Mooijaart, Simon99; Moon, Sanghoon80; Nabika, Toru182; Nadkarni, Girish N.38; Nadler, Jerry L.183; Nelis, Mari15; Neville, Matt J.11,184; Norris, Jill M.185; Ohyagi, Yasumasa186; Peters, Annette95,187,188; Peyser, Patricia A.51; Polasek, Ozren165,189; Qi, Qibin190; Raven, Dennis151; Reilly, Dermot F.191; Reiner, Alex192; Rivideneira, Fernando193; Roll, Kathryn21; Rudan, Igor194; Sabanayagam, Charumathi58,195; Sandow, Kevin21; Sattar, Naveed196; Schuermann, Annette95,197; Shi, Jinxiu198,199; Stringham, Heather M.42,43; Taylor, Kent D.21; Teslovich, Tanya M.200; Thuesen, Betina176; Timmers, Paul R. H. J.82,201; Tremoli, Elena135; Tsai, Michael Y.202; Uitterlinden, Andre193; van Dam, Rob M.40,41,178,203; van Heemst, Diana99; van Hylckama Vlieg, Astrid17; van Vliet-Ostaptchouk, Jana V.35; Vangipurapu, Jagadish204; Vestergaard, Henrik50,205; Wang, Tao190; Willems van Dijk, Ko206,207,208; Zemunik, Tatijana209; Abecasis, Goncalo R.43,184; Adair, Linda S.146,210; Aguilar-Salinas, Carlos Alberto211,212,213; Alarcon-Riquelme, Marta E.214,215; An, Ping216; Aviles-Santa, Larissa217; Becker, Diane M.218; Beilin, Lawrence J.219; Bergmann, Sven105,106,220; Bisgaard, Hans16; Black, Corri221; Boehnke, Michael42,43; Boerwinkle, Eric222,223; Boehm, Bernhard O.224,225,226; Bonnelykke, Klaus16; Boomsma, D. I.26,27; Bottinger, Erwin P.38,227,228; Buchanan, Thomas A.126,229,230; Canouil, Mickael231,232; Caulfield, Mark J.54,55; Chambers, John C.46,47,88,233,234; Chasman, Daniel I.23,235; Chen, Yii-Der Ida21; Cheng, Ching-Yu58,195; Collins, Francis S.139; Correa, Adolfo236; Cucca, Francesco100; de Silva, H. Janaka237; Dedoussis, George238; Elmstahl, Solve239; Evans, Michele K.240; Ferrannini, Ele241; Ferrucci, Luigi231,232,242; Florez, Jose C.109,243,244,245; Franks, Paul W.91,246; Frayling, Timothy M.1; Froguel, Philippe231,232,242; Gigante, Bruna247; Goodarzi, Mark O.248; Gordon-Larsen, Penny146,210; Grallert, Harald94,95; Grarup, Niels50; Grimsgaard, Sameline127; Groop, Leif249,250; Gudnason, Vilmundur112,251; Guo, Xiuqing21; Hamsten, Anders114; Hansen, Torben50; Hayward, Caroline201; Heckbert, Susan R.252; Horta, Bernardo L.74; Huang, Wei198,199; Ingelsson, Erik253; James, Pankow S.254; Järvelin, Marjo-Ritta255,256,257,258; Jonas, Jost B.259,260,261; Jukema, J. Wouter116,262; Kaleebu, Pontiano263; Kaplan, Robert190,192; Kardia, Sharon L. R.51; Kato, Norihiro115; Keinanen-Kiukaanniemi, Sirkka M.264,265; Kim, Bong-Jo80; Kivimaki, Mika266; Koistinen, Heikki A.267,268,269,270; Kooner, Jaspal S.47,233,234,271; Koerner, Antje122; Kovacs, Peter138,272; Kuh, Diana128; Kumari, Meena273; Kutalik, Zoltan106,274; Laakso, Markku167,168; Lakka, Timo A.275,276,277; Launer, Lenore J.62; Leander, Karin278; Li, Huaixing28; Lin, Xu28; Lind, Lars279; Lindgren, Cecilia12,280,281; Liu, Simin18; Loos, Ruth J. F.38,101; Magnusson, Patrik K. E.282,283; Mahajan, Anubha12,284; Metspalu, Andres15; Mook-Kanamori, Dennis O.17,285; Mori, Trevor A.219; Munroe, Patricia B.54,55; Njolstad, Inger127; O'Connell, Jeffrey R.96; Oldehinkel, Albertine J.151; Ong, Ken K.9; Padmanabhan, Sandosh286; Palmer, Colin N. A.; Palmer, Nicholette D.141; Pedersen, Oluf50; Pennell, Craig E.45; Porteous, David J.142,287,288; Pramstaller, Peter P.98; Province, Michael A.216; Psaty, Bruce M.52,252,289; Qi, Lu290; Raffel, Leslie J.291; Rauramaa, Rainer277; Redline, Susan56,57; Ridker, Paul M.23,292; Rosendaal, Frits R.17; Saaristo, Timo E.293,294; Sandhu, Manjinder295; Saramies, Jouko296; Schneiderman, Neil297; Schwarz, Peter95,140,298; Scott, Laura J.42,43; Selvin, Elizabeth37; Sever, Peter271; Shu, Xiao-ou89; Slagboom, P. Eline117; Small, Kerrin S.92; Smith, Blair H.299; Snieder, Harold35; Sofer, Tamar245,300; Sorensen, Thorkild I. A.7,8,50,301; Spector, Tim D.92; Stanton, Alice302; Steves, Claire J.92,303; Stumvoll, Michael138; Sun, Liang28; Tabara, Yasuharu81; Tai, E. Shyong40,41,178,304; Timpson, Nicholas J.7,8; Tonjes, Anke138; Tuomilehto, Jaakko305,306,307; Tusie, Teresa79,308; Uusitupa, Matti309; van der Harst, Pim24,120; van Duijn, Cornelia64,87; Vitart, Veronique201; Vollenweider, Peter310; Vrijkotte, Tanja G. M.129; Wagenknecht, Lynne E.311; Walker, Mark312; Wang, Ya X.260; Wareham, Nick J.9; Watanabe, Richard M.125,126,230; Watkins, Hugh12,150; Wei, Wen B.313; Wickremasinghe, Ananda R.314; Willemsen, Gonneke26,27; Wilson, James F.82,201; Wong, Tien-Yin58,195; Wu, Jer-Yuarn60; Xiang, Anny H.315; Yanek, Lisa R.218; Yengo, Loic316; Yokota, Mitsuhiro317; Zeggini, Eleftheria2,44,318,319; Zheng, Wei89; Zonderman, Alan B.62; Rotter, Jerome I.21; Gloyn, Anna L.11,12,184,320; McCarthy, Mark I.11,12,184,321,322,323; Dupuis, Josee25; Meigs, James B.109,245,324; Scott, Robert A.9; Prokopenko, Inga22,29; Leong, Aaron235,325,322,323; Liu, Ching-Ti25; Parker, Stephen C. J.6,326; Mohlke, Karen L.3; Langenberg, Claudia9; Wheeler, Eleanor2,9; Morris, Andrew P.12,327,328,329; Barroso, Ines1,2,9
Organizations: 1Univ Exeter, Med Sch, Exeter Ctr Excellence Diabet Res EXCEED, Genet Complex Traits, Exeter, Devon, England.
2Wellcome Sanger Inst, Dept Human Genet, Cambridge, England.
3Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA.
4Univ Massachusetts, Dept Biostat & Epidemiol, Amherst, MA 01003 USA.
5Univ Brest, INSERM, EFS, GGB,UMR 1078, Brest, France.
6Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
7Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England.
8Univ Bristol, Bristol Med Sch, Dept Populat Hlth Sci, Bristol, Avon, England.
9Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
10Shandong Univ, Sch Publ Hlth, Dept Biostat, Jinan, Peoples R China.
11Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet, Endocrinol & Metab, Oxford, England.
12Univ Oxford, Wellcome Ctr Human Genet, Oxford, England.
13RIKEN Ctr Integrat Med Sci, Lab Genom Diabet & Metab, Yokohama, Kanagawa, Japan.
14Inst Genet & Mol Med, Med Res Council, Human Genet Unit, Edinburgh, Midlothian, Scotland.
15Univ Tartu, Inst Genom, Estonian Genome Ctr, Tartu, Estonia.
16Univ Copenhagen, COPSAC, Copenhagen Prospect Studies Asthma Childhood, Herlev & Gentofte Hosp, Copenhagen, Denmark.
17Leiden Univ, Dept Clin Epidemiol, Med Ctr, Leiden, Netherlands.
18Brown Univ, Sch Publ Hlth, Dept Epidemiol, Providence, RI 02912 USA.
19City Univ Hong Kong, Dept Biomed Sci, Hong Kong, Peoples R China.
20City Univ Hong Kong, Dept Elect Engn, Hong Kong, Peoples R China.
21Harbor UCLA Med Ctr, Dept Pediat, Inst Translat Genom & Populat Sci, Lundquist Inst Biomed Innovat, Torrance, CA 90509 USA.
22Imperial Coll London, Dept Metab Digest & Reprod, London, England.
23Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.
24Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.
25Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
26Vrije Univ Amsterdam, Fac Behav & Movement Sci, Dept Biol Psychol, Amsterdam, Netherlands.
27Univ Amsterdam, Amsterdam Publ Hlth Res Inst, Med Ctr, Amsterdam, Netherlands.
28Univ Chinese Acad Sci, Shanghai Inst Nutr & Hlth, Chinese Acad Sci, CAS Key Lab Nutr Metab & Food Safety, Shanghai, Peoples R China.
29Univ Surrey, Dept Clin & Expt Res, 29Sect Stat Multi, Guildford, Surrey, England.
30Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
31SYNLAB Holding Deutschland GmbH, SYNLAB Acad, Mannheim, Germany.
32Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria.
33Heidelberg Univ, Med Fac Mannheim, Dept Med Nephrol 5, Hypertensiol,Rheumatol,Endocrinol,Diabetol, Mannheim, Baden Wurttembe, Germany.
34Metropolitan Autonomous Univ, Dept Econ, Mexico City, DF, Mexico.
35Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
36Univ N Carolina, Gillings Sch Global Publ Hlth, CVD Genet Epidemiol Computat Lab, Chapel Hill, NC 27515 USA.
37Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
38Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
39Hasso Plattner Inst, HPI Digital Hlth Ctr, Digital Hlth & Personalized Med, Potsdam, Germany.
40Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.
41Natl Univ Hlth Syst, Singapore, Singapore.
42Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
43Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.
44German Res Ctr Environm Hlth, Inst Translat Genom, Helmholtz Zentrum Munchen, Neuherberg, Germany.
45Univ Newcastle, Coll Hlth Med & Wellbeing, Sch Med & Publ Hlth, Newcastle, NSW, Australia.
46Imperial Coll London, Dept Epidemiol & Biostat, London, England.
47London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, London, England.
48Steno Diabet Ctr Copenhagen, Gentofte, Denmark.
49Univ Copenhagen, Dept Biol, Bioinformat Ctr, Copenhagen, Denmark.
50Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.
51Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
52Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
53Broad Inst, Metab Program, Program Med & Populat Genet, Cambridge, MA USA.
54Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, Dept Clin Pharmacol, London, England.
55Queen Mary Univ London, NIHR Barts Cardiovasc Biomed Res Ctr, London, England.
56Brigham & Womens Hosp, Dept Med Sleep & Circadian Disorders, 75 Francis St, Boston, MA 02115 USA.
57Harvard Med Sch, Dept Med, Sleep Med, Boston, MA 02115 USA.
58Singapore Natl Eye Ctr, Singapore Eye Res Inst, Ocular Epidemiol, Singapore, Singapore.
59Natl Univ Singapore, Dept Ophthalmol, Singapore, Singapore.
60Acad Sinica, Inst Biomed Sci, Taipei, Taiwan.
61Univ Calif San Diego, Dept Epidemiol, Herbert Wertheim Sch Publ Hlth & Human Longev Sci, La Jolla, CA 92093 USA.
62NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA.
63Natl Hlth Res Inst, Inst Populat Hlth Sci, Miaoli, Taiwan.
64Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
65Univ N Carolina, Dept Stat, Chapel Hill, NC 27515 USA.
66UCL, Inst Cardiovasc Sci, London, England.
67Uganda Med Informat Ctr UMIC, MRC UVRI, Entebbe, Uganda.
68London Sch Hyg & Trop Med, Uganda Res Unit, Entebbe, Uganda.
69London Sch Hyg & Trop Med, London, England.
70NABDA FMST, Ctr Genom Res & Innovat, H3Africa Bioinformat Network H3ABioNet Node, Abuja, Nigeria.
71Bioinfosol, Seville, Spain.
72Uppsala Univ, Dept Med Sci, Mol Epidemiol & Sci Life Lab, Uppsala, Sweden.
73Univ Auckland, Sci Ctr, Dept Stat, Auckland, New Zealand.
74Univ Fed Pelotas, Postgrad Program Epidemiol, Pelotas, RS, Brazil.
75Vanderbilt Univ, Med Ctr, Dept Med, Epidemiol, Nashville, TN USA.
76Tulane Univ, Dept Epidemiol, Obes Res Ctr, New Orleans, LA 70118 USA.
77Peking Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Beijing, Peoples R China.
78Natl Council Sci & Technol, Mol Biol & Genom Med Unit, Mexico City, DF, Mexico.
79Natl Inst Med Sci & Nutr, Mol Biol & Genom Med Unit, Mexico City, DF, Mexico.
80Natl Inst Hlth, Dept Precis Med, Div Genome Sci, Cheongju, South Korea.
81Kyoto Univ, Ctr Genom Med, Grad Sch Med, Kyoto, Japan.
82Univ Edinburgh, Usher Inst, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland.
83Univ Edinburgh, Queens Med Res Inst, Ctr Cardiovasc Sci, Edinburgh, Midlothian, Scotland.
84Univ Colorado, Dept Med, Div Biomed Informat & Personalized Med, Anschutz Med Campus, Denver, CO USA.
85Wake Forest Sch Med, Dept Biostat & Data Sci, Winston Salem, NC 27101 USA.
86Univ Utah, Dept Med, Div Nephrol & Hypertens, Salt Lake City, UT 84112 USA.
87Univ Oxford, Nuffield Dept Populat Hlth, Oxford, England.
88Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore.
89Vanderbilt Univ, Med Ctr, Dept Med, Div Epidemiol,Vanderbilt Epidemiol Ctr, Nashville, TN USA.
90Univ Bergen, Ctr Diabet Res, Dept Clin Sci, Bergen, Norway.
91Lund Univ, Diabet Ctr, Dept Clin Sci, Malmo, Sweden.
92Kings Coll London, Sch Life Course Sci, Dept Twin Res & Genet Epidemiol, London, England.
93Guys & St Thomas NHS Fdn Trust, NIHR Biomed Res Ctr, London, England.
94Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Inst Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.
95German Ctr Diabet Res DZD, Neuherberg, Germany.
96Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
97Nagoya Univ, Dept Integrated Sci, Publ Hlth Informat Unit, Grad Sch Med, Nagoya, Aichi, Japan.
98Eurac Res, Inst Biomed, Bolzano, Italy.
99Leiden Univ, Sect Gerontol & Geriatr, Dept Internal Med, Med Ctr, Leiden, Netherlands.
100CNR, Ist Ric Genet & Biomed IRGB, Monserrato, Italy.
101Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst Personalized Med, New York, NY 10029 USA.
102Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA.
103Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
104Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA.
105Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland.
106Swiss Inst Bioinformat, Lausanne, Switzerland.
107Harvard Med Sch, Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02115 USA.
108Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
109Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
110Uppsala Univ, Sci Life Lab, Dept Cell & Mol Biol, Natl Bioinformat Infrastruct Sweden, Uppsala, Sweden.
111Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
112Ice Heart Assoc, Kopavogur, Iceland.
113Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland.
114Karolinska Inst, Dept Med Solna, Cardiovasc Med, Stockholm, Sweden.
115Natl Ctr Global Hlth & Med, Tokyo, Japan.
116Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands.
117Leiden Univ, Dept Biomed Data Sci, Mol Epidemiol, Med Ctr, Leiden, Netherlands.
118Delft Univ Technol, Dept Pattern Recognit & Bioinformat, Delft, Netherlands.
119Leiden Univ, Leiden Computat Biol Ctr, Dept Biomed Data Sci, Med Ctr, Leiden, Netherlands.
120Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
121Genom PLC, Oxford, England.
122Univ Leipzig, Univ Childrens Hosp Leipzig, Ctr Pediat Res, Med Ctr, Leipzig, Germany.
123Huazhong Univ Sci & Technol, Sch Publ Hlth, Tongji Med Coll, Dept Epidemiol & Biostat, Wuhan, Peoples R China.
124Agcy Sci Res & Technol, Genome Inst Singapore, Singapore, Singapore.
125Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90007 USA.
126Univ Southern Calif, Keck Sch Med, Diabet & Obes Res Inst, Los Angeles, CA 90007 USA.
127UIT Arctic Univ Norway, Dept Community Med, Fac Hlth Sci, Tromso, Norway.
128UCL, MRC Unit Lifelong Hlth & Ageing, London, England.
129Univ Amsterdam, Amsterdam Publ Hlth Res Inst, Dept Publ Hlth, Med Ctr, Amsterdam, Netherlands.
130Univ Amsterdam, Amsterdam Publ Hlth Res Inst, Dept Clin Epidemiol Biostat & Bioinformat, Med Ctr, Amsterdam, Netherlands.
131Univ Cambridge, Sch Clin Med, Dept Publ Hlth & Primary Care, Cambridge, England.
132Univ Copenhagen, Dept Nutr Exercise & Sports, Fac Sci, Copenhagen, Denmark.
133Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands.
134Univ Milan, Dept Med Biotechnol & Translat Med, Milan, Italy.
135IRCCS, Ctr Cardiol Monzino, Milan, Italy.
136Cedars Sinai Med Ctr, Diabet & Obes Res Inst, Los Angeles, CA 90048 USA.
137Wake Forest Sch Med, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC 27101 USA.
138Univ Leipzig, Med Dept Endocrinol 3, Med Ctr, Nephrol,Rheumatol, Leipzig, Germany.
139NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA.
140Tech Univ Dresden, Fac Med Carl Gustav Carus, Dept Prevent & Care Diabet, Dresden, Germany.
141Wake Forest Sch Med, Dept Biochem, Winston Salem, NC 27101 USA.
142Univ Edinburgh, Inst Genet & Mol Med, Western Gen Hosp, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland.
143Univ Edinburgh, Usher Inst, Edinburgh, Midlothian, Scotland.
144Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan.
145Natl Taiwan Univ, Grad Inst Med Genom & Prote, Taipei, Taiwan.
146Univ N Carolina, Dept Nutr, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27515 USA.
147UCL, Inst Cardiovasc Sci, Dept Populat Sci & Expt Med, London, England.
148Harokopio Univ Athens, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens, Greece.
149Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
150Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford, England.
151Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathy & Emot Regulat, Dept Psychiat, Groningen, Netherlands.
152Heinrich Heine Univ Dusseldorf, German Diabet Ctr, Leibniz Ctr Diabet Res, Inst Clin Diabetol, Dusseldorf, Germany.
153Heinrich Heine Univ Dusseldorf, Med Fac, Div Endocrinol & Diabetol, Dusseldorf, Germany.
154German Ctr Diabet Res DZD, Dusseldorf, Germany.
155Tri Serv Gen Hosp, Internal Med Endocrine & Metab, Taipei, Taiwan.
156Natl Def Med Ctr, Sch Med, Taipei, Taiwan.
157Ohio State Univ, Wexner Med Ctr, Internal Med Endocrinol Diabet & Metab, Diabet & Metab Res Ctr, Columbus, OH 43210 USA.
158Jichi Med Univ, Sch Med, Dept Environm & Prevent Med, Shimotsuke, Tochigi, Japan.
159Ehime Univ, Dept Antiaging Med, Grad Sch Med, Toon, Japan.
160Univ Southern Denmark, Natl Inst Publ Hlth, Odense, Denmark.
161Johns Hopkins Univ, Sch Med, Dept Med Endocrinol Diabet & Metab, Baltimore, MD USA.
162City Hope Natl Med Ctr, Beckman Res Inst, Clin Diabet Endocrinol & Metab, Translat Res & Cellular Therapeut, Duarte, CA USA.
163Osaka Univ, Dept Clin Gene Therapy, Grad Sch Med, Suita, Osaka, Japan.
164Osaka Univ, Dept Geriatr & Gen Med, Grad Sch Med, Suita, Osaka, Japan.
165Univ Split, Dept Publ Hlth, Sch Med, Split, Croatia.
166Univ Eastern Finland, Bioinformat Ctr, Inst Biomed, Kuopio, Finland.
167Univ Eastern Finland, Dept Med, Kuopio, Finland.
168Kuopio Univ Hosp, Kuopio, Finland.
169Univ San Carlos, USC Off Populat Studies Fdn, Cebu, Philippines.
170Univ San Carlos, Dept Anthropol Sociol & Hist, Cebu, Philippines.
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174Natl Yang Ming Univ, Natl Def Med Ctr, Taipei, Taiwan.
175Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland.
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185Univ Colorado, Colorado Sch Publ Hlth, Anschutz Med Campus, Aurora, CO USA.
186Ehime Univ, Grad Sch Med, Dept Geriatr Med & Neurol, Toon, Japan.
187Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany.
188Ludwig Maximilians Univ Munchen, Inst Med Informat Proc Biometry & Epidemiol, Munich, Germany.
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195Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program Eye ACP, Singapore, Singapore.
196Univ Glasgow, Inst Cardiovasc & Med Sci, BHF Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland.
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201Univ Edinburgh, Inst Genet & Canc, Med Res Council, Human Genet Unit, Edinburgh, Midlothian, Scotland.
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204Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland.
205Bornholms Hosp, Dept Med, Ronne, Denmark.
206Leiden Univ, Div Endocrinol, Dept Internal Med, Med Ctr, Leiden, Netherlands.
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213Inst Tecnol & Estudios Super Monterrey Tec Salud, Monterrey, Mexico.
214Univ Granada, Andalusian Govt Ctr Genom & Oncol Res GENYO, Dept Med Gen, Pfizer, Granada, Spain.
215Karolinska Inst, Inst Environm Med, Chron Inflammatory Dis, Solna, Sweden.
216Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
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218Johns Hopkins Univ, Sch Med, Dept Med, Gen Internal Med, Baltimore, MD 21205 USA.
219Univ Western Australia, Med Sch, Royal Perth Hosp Unit, Perth, Australia.
220Univ Cape Town, Dept Integrat Biomed Sci, Cape Town, South Africa.
221Univ Aberdeen, Sch Med Med Sci & Nutr, Aberdeen Ctr Hlth Data Sci, Aberdeen, Scotland.
222Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA.
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224Univ Ulm, Grad Sch Mol Endocrinol & Diabet, Div Endocrinol & Diabet, Ulm, Germany.
225Nanyang Technol Univ, LKC Sch Med, Singapore, Singapore.
226Imperial Coll London, London, England.
227Icahn Sch Med Mt Sinai, Hasso Plattner Inst Digital Hlth Mt Sinai, New York, NY 10029 USA.
228Univ Potsdam, Hasso Plattner Inst, Digital Hlth Ctr, Potsdam, Germany.
229Univ Southern Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90007 USA.
230Univ Southern Calif, Keck Sch Med, Dept Physiol & Neurosci, Los Angeles, CA 90007 USA.
231Univ Lille, European Inst Diabet EGID, INSERM, CNRS,UMR 8199,UMR 1283, Lille, France.
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233Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England.
234Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England.
235Harvard Med Sch, Boston, MA 02115 USA.
236Univ Mississippi, Med Ctr, Dept Med, Jackson Heart Study, Jackson, MS 39216 USA.
237Univ Kelaniya, Dept Med, Fac Med, Ragama, Sri Lanka.
238Harokopio Univ Athens, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Kallithea, Greece.
239Lund Univ, Dept Clin Sci, Malmo, Sweden.
240NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
241CNR Inst Clin Physiol, Pisa, Italy.
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244Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA.
245Harvard Med Sch, Dept Med, Boston, MA 02115 USA.
246Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
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248Cedars Sinai Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA.
249Lund Univ, Diabet Ctr, Lund, Sweden.
250Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland.
251Univ Iceland, Sch Hlth Sci, Fac Med, Reykjavik, Iceland.
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253Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
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255Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London, England.
256Univ Oulu, Ctr Life Course Hlth Res, Fac Med, Oulu, Finland.
257Oulu Univ Hosp, Unit Primary Hlth Care, OYS, Oulu, Finland.
258Brunel Univ London, Coll Hlth & Life Sci, Dept Life Sci, London, England.
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271Imperial Coll London, Natl Heart & Lung Inst, London, England.
272Univ Leipzig, IFB Adipos Dis, Med Ctr, Leipzig, Germany.
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275Univ Eastern Finland, Sch Med, Inst Biomed, Kuopio, Finland.
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279Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
280Univ Oxford, Big Data Inst, Nuffield Dept Med, Oxford, England.
281Univ Oxford, Nuffield Dept Womens & Reprod Hlth, Oxford, England.
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Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 3.3 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2022030422054
Language: English
Published: Springer Nature, 2021
Publish Date: 2022-03-04
Description:

Abstract

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.

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Series: Nature genetics
ISSN: 1061-4036
ISSN-E: 1546-1718
ISSN-L: 1061-4036
Volume: 53
Issue: 6
Pages: 840 - 860
DOI: 10.1038/s41588-021-00852-9
OADOI: https://oadoi.org/10.1038/s41588-021-00852-9
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Subjects:
Funding: NFBC1966 has received core funding for data generation and curation from the Academy of Finland (project grants 104781, 120315, 129269, 1114194, 24300796, 85547, 285547 (EGEA)), University Hospital Oulu, Finland (75617), ERDF European Regional Development Fund Grant no. 539/2010A31592 and the EU H2020--PHC-2014 DynaHEALTH action (grant no. 633595). The NFBC1966 is also funded by EU-H2020 LifeCycle Action (grant no. 733206), EU-H2020 EDCMET (grant no. 825762), EU-H2020 EUCAN Connect (grant no 824989), EU H2020-MSCA-ITN-2016 CAPICE Marie Sklodowska-Curie grant (grant no. 721567) and the Medical Research Council, UK (grants no. MR/M013138/1,MRC/BBSRC MR/S03658X/1 (JPI HDHL)).
EU Grant Number: (633595) DYNAHEALTH - Understanding the dynamic determinants of glucose homeostasis and social capability to promote Healthy and active aging
(733206) LIFECYCLE - Early-life stressors and LifeCycle health
(825762) EDCMET - Metabolic effects of Endocrine Disrupting Chemicals: novel testing METhods and adverse outcome pathways
(824989) EUCAN-Connect - A federated FAIR platform enabling large-scale analysis of high-value cohort data connecting Europe and Canada in personalized health
Academy of Finland Grant Number: 285547
Detailed Information: 285547 (Academy of Finland Funding decision)
Copyright information: © The Author(s), under exclusive licence to Springer Nature America, Inc. 2021. This is a post-peer-review, pre-copyedit version of an article published in Nat Genet. The final authenticated version is available online at https://doi.org/10.1038/s41588-021-00852-9.