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dc.contributor.authorWheeler, Eleanor
dc.contributor.authorLeong, Aaron
dc.contributor.authorLiu, Ching-Ti
dc.contributor.authorHivert, Marie-France
dc.contributor.authorStrawbridge, Rona J.
dc.contributor.authorPodmore, Clara
dc.contributor.authorLi, Man
dc.contributor.authorYao, Jie
dc.contributor.authorSim, Xueling
dc.contributor.authorHong, Jaeyoung
dc.contributor.authorChu, Audrey Y.
dc.contributor.authorZhang, Weihua
dc.contributor.authorWang, Xu
dc.contributor.authorChen, Peng
dc.contributor.authorMaruthur, Nisa M.
dc.contributor.authorPorneala, Bianca C.
dc.contributor.authorSharp, Stephen J.
dc.contributor.authorJia, Yucheng
dc.contributor.authorKabagambe, Edmond Kato
dc.contributor.authorChang, Li-Ching
dc.contributor.authorChen, Wei-Min
dc.contributor.authorElks, Cathy E.
dc.contributor.authorEvans, Daniel S.
dc.contributor.authorFan, Qiao
dc.contributor.authorGiulianini, Franco
dc.contributor.authorGo, Min Jin
dc.contributor.authorHottenga, Jouke-Jan
dc.contributor.authorHu, Yao
dc.contributor.authorJackson, Anne U.
dc.contributor.authorKanoni, Stavroula
dc.contributor.authorKim, Young Jin
dc.contributor.authorKleber, Marcus E.
dc.contributor.authorLadenvall, Claes
dc.contributor.authorLecoeur, Cecile
dc.contributor.authorLim, Sing-Hui
dc.contributor.authorLu, Yingchang
dc.contributor.authorMahajan, Anubha
dc.contributor.authorMarzi, Carola
dc.contributor.authorNalls, Mike A.
dc.contributor.authorNavarro, Pau
dc.contributor.authorNolte, Ilja M.
dc.contributor.authorRose, Lynda M.
dc.contributor.authorRybin, Denis V.
dc.contributor.authorSanna, Serena
dc.contributor.authorShi, Yuan
dc.contributor.authorStram, Daniel O.
dc.contributor.authorTakeuchi, Fumihiko
dc.contributor.authorTan, Shu Pei
dc.contributor.authorvan der Most, Peter J.
dc.contributor.authorVan Vliet-Ostaptchouk, Jana V.
dc.contributor.authorWong, Andrew
dc.contributor.authorYengo, Loic
dc.contributor.authorZhao, Wanting
dc.contributor.authorGoel, Anuj
dc.contributor.authorMartinez Larrad, Maria Teresa
dc.contributor.authorRadke, Dörte
dc.contributor.authorSalo, Perttu
dc.contributor.authorTanaka, Toshiko
dc.contributor.authorvan Iperen, Erik P.A.
dc.contributor.authorAbecasis, Goncalo
dc.contributor.authorAfaq, Saima
dc.contributor.authorAlizadeh, Behrooz Z.
dc.contributor.authorBertoni, Alain G.
dc.contributor.authorBonnefond, Amelie
dc.contributor.authorBöttcher, Yvonne
dc.contributor.authorBottinger, Erwin P.
dc.contributor.authorCampbell, Harry
dc.contributor.authorCarlson, Olga D.
dc.contributor.authorChen, Chien-Hsiun
dc.contributor.authorCho, Yoon Shin
dc.contributor.authorGarvey, W. Timothy
dc.contributor.authorGieger, Christian
dc.contributor.authorGoodarzi, Mark O.
dc.contributor.authorGrallert, Harald
dc.contributor.authorHamsten, Anders
dc.contributor.authorHartman, Catharina A.
dc.contributor.authorHerder, Christian
dc.contributor.authorHsiung, Chao Agnes
dc.contributor.authorHuang, Jie
dc.contributor.authorIgase, Michiya
dc.contributor.authorIsono, Masato
dc.contributor.authorKatsuya, Tomohiro
dc.contributor.authorKhor, Chiea-Chuen
dc.contributor.authorKiess, Wieland
dc.contributor.authorKohara, Katsuhiko
dc.contributor.authorKovacs, Peter
dc.contributor.authorLee, Juyoung
dc.contributor.authorLee, Wen-Jane
dc.contributor.authorLehne, Benjamin
dc.contributor.authorLi, Huaixing
dc.contributor.authorLiu, Jianjun
dc.contributor.authorLobbens, Stephane
dc.contributor.authorLuan, Jian'an
dc.contributor.authorLyssenko, Valeriya
dc.contributor.authorMeitinger, Thomas
dc.contributor.authorMiki, Tetsuro
dc.contributor.authorMiljkovic, Iva
dc.contributor.authorMoon, Sanghoon
dc.contributor.authorMulas, Antonella
dc.contributor.authorMüller, Gabriele
dc.contributor.authorMüller-Nurasyid, Martina
dc.contributor.authorNagaraja, Ramaiah
dc.contributor.authorNauck, Matthias
dc.contributor.authorPankow, James S.
dc.contributor.authorPolasek, Ozren
dc.contributor.authorProkopenko, Inga
dc.contributor.authorRamos, Paula S.
dc.contributor.authorRasmussen-Torvik, Laura
dc.contributor.authorRathmann, Wolfgang
dc.contributor.authorRich, Stephen S.
dc.contributor.authorRobertson, Neil R.
dc.contributor.authorRoden, Michael
dc.contributor.authorRoussel, Ronan
dc.contributor.authorRudan, Igor
dc.contributor.authorScott, Robert A.
dc.contributor.authorScott, William R.
dc.contributor.authorSennblad, Bengt
dc.contributor.authorSiscovick, David S.
dc.contributor.authorStrauch, Konstantin
dc.contributor.authorSun, Liang
dc.contributor.authorSwertz, Morris
dc.contributor.authorTajuddin, Salman M.
dc.contributor.authorTaylor, Kent D.
dc.contributor.authorTeo, Yik-Ying
dc.contributor.authorTham, Yih Chung
dc.contributor.authorTönjes, Anke
dc.contributor.authorWareham, Nicholas J.
dc.contributor.authorWillemsen, Gonneke
dc.contributor.authorWilsgaard, Tom
dc.contributor.authorHingorani, Aroon D.
dc.contributor.authorEgan, Josephine
dc.contributor.authorFerrucci, Luigi
dc.contributor.authorHovingh, G. Kees
dc.contributor.authorJula, Antti
dc.contributor.authorKivimäki, Mika
dc.contributor.authorKumari, Meena
dc.contributor.authorNjølstad, Inger
dc.contributor.authorPalmer, Colin N.A.
dc.contributor.authorSerrano Rios, Manuel
dc.contributor.authorStumvoll, Michael
dc.contributor.authorWatkins, Hugh
dc.contributor.authorAung, Tin
dc.contributor.authorBlüher, Matthias
dc.contributor.authorBoehnke, Michael
dc.contributor.authorBoomsma, Dorret I.
dc.contributor.authorBornstein, Stefan R.
dc.contributor.authorChambers, John C.
dc.contributor.authorChasman, Daniel I.
dc.contributor.authorChen, Yii-Der Ida
dc.contributor.authorChen, Yduan-Tsong
dc.contributor.authorCheng, Ching-Yu
dc.contributor.authorCucca, Francesco
dc.contributor.authorde Geus, Eco J.C.
dc.contributor.authorDeloukas, Panos
dc.contributor.authorEvans, Michele K.
dc.contributor.authorFornage, Myriam
dc.contributor.authorFriedlander, Yechiel
dc.contributor.authorFroguel, Philippe
dc.contributor.authorGroop, Leif
dc.contributor.authorGross, Myron D.
dc.contributor.authorHarris, Tamara B.
dc.contributor.authorHayward, Caroline
dc.contributor.authorHeng, Chew-Kiat
dc.contributor.authorIngelsson, Erik
dc.contributor.authorKato, Norihiro
dc.contributor.authorKim, Bong-Jo
dc.contributor.authorKoh, Woon-Puay
dc.contributor.authorKooner, Jaspal S.
dc.contributor.authorKorner, Antje
dc.contributor.authorKuh, Diana
dc.contributor.authorKuusisto, Johanna
dc.contributor.authorLaakso, Markku
dc.contributor.authorLin, Xu
dc.contributor.authorLiu, Yongmei
dc.contributor.authorLoos, Ruth J.F.
dc.contributor.authorMagnusson, Patrik K.E.
dc.contributor.authorMärz, Winfried
dc.contributor.authorMcCarthy, Mark I.
dc.contributor.authorOldehinkel, Albertine J.
dc.contributor.authorOng, Ken K.
dc.contributor.authorPedersen, Nancy L.
dc.contributor.authorPereira, Mark A.
dc.contributor.authorPeters, Annette
dc.contributor.authorRidker, Paul M.
dc.contributor.authorSabanayagam, Charumathi
dc.contributor.authorSale, Michele
dc.contributor.authorSaleheen, Danish
dc.contributor.authorSaltevo, Juha
dc.contributor.authorSchwarz, Peter E.H.
dc.contributor.authorSheu, Wayne H.-H.
dc.contributor.authorSnieder, Harold
dc.contributor.authorSpector, Timothy D.
dc.contributor.authorTabara, Yasuharu
dc.contributor.authorTuomilehto, Jaakko
dc.contributor.authorVan Dam, Rob M.
dc.contributor.authorWilson, James G
dc.contributor.authorWilson, James F.
dc.contributor.authorWolffenbuttel, Bruce H.R.
dc.contributor.authorWong, Tien Yin
dc.contributor.authorWu, Jer-Yuarn
dc.contributor.authorYuan, Jian-Min
dc.contributor.authorZonderman, Alan B.
dc.contributor.authorSoranzo, Nicole
dc.contributor.authorGuo, Xiuqing
dc.contributor.authorFlorez, Jose C.
dc.contributor.authorSladek, Robert
dc.contributor.authorDupuis, Josée
dc.contributor.authorMorris, Andrew P.
dc.contributor.authorTai, E-Shyong
dc.contributor.authorSelvin, Elizabeth
dc.contributor.authorRotter, Jerome I.
dc.contributor.authorLangenberg, Claudia
dc.contributor.authorBarroso, Inês
dc.contributor.authorMeigs, James B.
dc.date.accessioned2018-07-05T10:45:32Z
dc.date.available2018-07-05T10:45:32Z
dc.date.issued2017-09-12
dc.description.abstract<b>Background:</b> <br> Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes. <br><b>Methods & findings: </b> <br> Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04–1.06, per HbA1c-raising allele, p = 3 × 10−29); whereas GS-E was not (OR = 1.00, 95% CI 0.99–1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66–0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38–0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI0.55–0.74) of African American adults with T2D to remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants.<br> <b>Conclusions: </b> <br> As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.en_US
dc.description.sponsorshipThe Ministry of Education, Culture, Sports, Science, and Technology, Japan: 24390084, 21390099, 20390185; Science and Technology Incubation Program in Advanced Regions; Japan Science and Technology Agency; The Japan Atherosclerosis Prevention Fund; The Takeda Medical Research Foundation; National Cardiovascular Research Grants. VIDI grant provided by the Dutch Science Organisation: 016.156.445; CardioVascular Research Initiative: CVON2011-19; Wellcome Trust: WT098017; National Heart, Lung, and Blood Institute contracts: HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C, R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute: U01HG004402; National Institutes of Health: HHSN268200625226C; The National Institutes of Health and NIH Roadmap for Medical Research: UL1RR025005, 2R01DK089174 and K24DK106414, R21DK080294; National Heart, Lung, and Blood Institute: T32-HL007024; The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID); National Human Genome Research Institute (NHGRI); National Institute of Child Health and Human Development (NICHD); Juvenile Diabetes Research Foundation International (JDRF); U01 DK062418. T1DGC GWAS data were deposited by the Diabetes and Inflammation Laboratory; Cambridge Institute for Medical Research (CIMR); University of Cambridge Juvenile Diabetes Research Foundation International; The Wellcome Trust; The National Institute for Health Research Cambridge Biomedical Research Centre; The CIMR is in receipt of a Wellcome Trust Strategic Award: 079895. Medical Research Council: G0000934 The Wellcome Trust: 068545/Z/02. The Wellcome Trust: 076113/B/04/Z. The Magnus Bergvall foundation; The Foundation for old servants; The Andrea and Charles Bronfman Philanthropies; The Intramural Research Program of the NIH, National Institute on Aging; The Core Research for Evolutional Science and Technology (CREST) from the Japan Science Technology Agency; The Program for Promotion of Fundamental Studies in Health Sciences; National Institute of Biomedical Innovation Organization (NIBIO); National Center for Global Health and Medicine (NCGM); The National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham: HHSN268201300025C & HHSN268201300026C; Northwestern University: HHSN268201300027C; University of Minnesota: HHSN268201300028C; Kaiser Foundation Research Institute: HHSN268201300029C; Johns Hopkins University School of Medicine: HHSN268200900041C The Intramural Research Program of the National Institute on Aging; The National Human Genome Research Institute: U01-HG-004729, U01-HG-004446, and U01-HG-004424; The Wellcome Trust: 097451/Z/11/Z; The Medical Research Council UK; The Croatian Ministry of Science, Education and sports: grant 216-1080315-0302 Croatian Science Foundation: 8875; INSERM contracts with CNAMTS; Lilly; Novartis Pharma; Sanofi-Aventis; INSERM (Réseaux en Santé Publique, Interactions entre les déterminants de la santé); Cohortes Santé TGIR; The Association Diabète Risque Vasculaire; The Fédération Française de Cardiologie; LA Fondation de France; ALFEDIAM; Société francophone du diabète; ONIVINS; Abbott; Ardix Medical; Bayer Diagnostics; Becton Dickinson; Cardionics; Merck Santé; Novo Nordisk; Pierre Fabre; Roche; Topcon; NHS Blood and Transplant (UK); The NIHR Biomedical Research Centre Programme at Oxford The National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Donor Health and Genomics. The DIAGEN study was supported by the Commission of the European Communities; Directorate C - Public Health and Risk Assessment, Health & Consumer Protection: 2004310; The Dresden University of Technology Funding Grant, Med Drive; The Academy of Finland: 117844 and 40758, 211497, and 118590 (MU); The EVO funding of the Kuopio University Hospital from Ministry of Health and Social Affairs: 5254; Finnish Funding Agency for Technology and Innovation: 40058/07; Nordic Centre of Excellence on ‘Systems biology in controlled dietary interventions and cohort studies, SYSDIET: 070014; The Finnish Diabetes Research Foundation; Yrjö Jahnsson Foundation; 56358, Sigrid Juselius Foundation: 70103/06; TEKES: 40058/07; NIH: 1R01DK106236-01A1; The Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health; Boston University School of Medicine; The National Heart, Lung and Blood Institute's Framingham Heart Study: N01‐HC‐25195; Contract with Affymetrix, Inc for genotyping services: N02‐HL‐6‐4278; National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK): R01 DK078616, K24 DK080140, U01 DK085526. The hospital districts of Pirkanmaa; Southern Ostrobothnia; North Ostrobothnia; Central Finland and Northern Savo; the Finnish National Public Health Institute; the Finnish Diabetes Association; the Ministry of Social Affairs and Health in Finland; Finland’s Slottery Machine Association; The Academy of Finland: 129293 Commission of the European Communities, Directorate C-Public Health [grant agreement no. 2004310] The Wellcome Trust (Biomedical Collections: GR072960). The Intramural Research Program of the NIH; National Institute on Aging; The National Center on Minority Health and Health Disparities: Z01-AG000513 NIA: N01AG62101, N01AG62103 and N01AG62106; NIA: 1R01AG032098-01A1 The National Institutes of Health to The Johns Hopkins University: HHSN268200782096C; The Intramural Research Program of the NIH, National Institute on Aging. FP6 programme: LSHM_CT_2006_037197 (not found in Cordis' project & results) MIM: Wellcome Trust: 083270/Z/07/Z, MRC: G0601261; PWF: Swedish Research Council; Novo Nordisk; Swedish Diabetes Association; Swedish Heart-Lung Foundation; German Cancer Aid; German Ministry of Research (BMBF); Cancer Research UK: C8221/A19170; Medical Research Council: MR/M012190/1; Health Research Fund (FIS) of the Spanish Ministry of Health; Murcia Regional Government: 6236); Swedish Research Council; Danish Cancer Society; Compagnia di San Paolo; Asturias Regional Government; The Västerboten County Council; The Dutch Ministry of Public Health; Welfare and Sports; Netherlands Cancer Registry; Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland); World Cancer Research Fund (WCRF); Statistics Netherlands; Sicilian Regional Government; AIRE -ONLUS Ragusa; Imperial College Biomedical Research Centre; Wellcome Trust: WT098051 The National Institute of Health: R01-DK097084; The National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities: HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C; Diabetes Funds Junior Fellowship from the Dutch Diabetes Research Foundation: 2013.81.1673; (KARE) Korea Centers for Disease Control and Prevention: 4845–301, 4851–302, 4851–307; The Korea National Institute of Health: 2014-NI73001-00; The Helmholtz Zentrum München – German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria; The BMBF to the German Center for Diabetes Research (DZD); The Ministry of Innovation, Science, Research and Technology of the state North Rhine-Westphalia (Düsseldorf, Germany); The Federal Ministry of Education and Research (German Obesity Biomaterial Bank: FKZ 01GI1128); The Federal Ministry of Education and Research (BMBF), Germany, FKZ: 01EO1501 (K6e/2, AD2-060E). The Collaborative Research Center funded by the German Research Foundation: CRC 1052; B01, B03; The German Diabetes Association; DHFD (Diabetes Hilfs- und Forschungsfonds Deutschland); Boehringer Ingelheim Foundation; Integrated Research and Treatment Centre (IFB) Adiposity Diseases FKZ: 01EO1001; The German Research Foundation for the Clinical Research Center “Obesity Mechanisms”: CRC1052/1 C05; The European Union, by the European Regional Development Fund (ERDF); The Free State of Saxony within the framework of the excellence initiative; The Netherlands Organization of Scientific Research NWO: 175.010.2007.006; The Economic Structure Enhancing Fund (FES) of the Dutch government; The Ministry of Economic Affairs; The Ministry of Education, Culture and Science; The Ministry for Health, Welfare and Sports; The Northern Netherlands Collaboration of Provinces (SNN); The Province of Groningen; University Medical Center Groningen; The University of Groningen; Dutch Kidney Foundation and Dutch Diabetes Research Foundation; The National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre Imperial College Healthcare NHS Trust; The British Heart Foundation: SP/04/002; The Medical Research Council: G0601966, G0700931; The Wellcome Trust: 084723/Z/08/Z; The NIHR: RP-PG-0407-10371; Action on Hearing Loss (G51); The INTERREG IV Oberrhein Program: Project A28; Te European Regional Development Fund (ERDF); The Wissenschaftsoffensive TMO; Data Tecnica International National Institute on Aging, NIH; Wellcome Trust: 090532, 098381; The National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support for MESA is provided by contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-001079, UL1-TR-000040, and DK063491; The Academy of Finland: 124243); The Finnish Heart Foundation; The Finnish Diabetes Foundation; Tekes: 1510/31/06; The UK Medical Research Council: K013351; The Major Project of the Ministry of Science and Technology of China: 2016YFC1304903; The National Natural Science Foundation of China: 30930081, 81471013, and 81170734; The Wellcome Trust: WT098051, WT091310; The National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Donor Health and Genomics at the University of Cambridge in partnership with NHS Blood and Transplant (NHSBT); The Medical Research Council: MC_UU_12019/1; The British Heart Foundation: RG/10/12/28456; The Wellcome Trust: 088869/B/09/Z; The Netherlands Organization for Scientific Research: 904-61-090, 985-10-002, 904-61-193,480-04-004, 400-05-717, Addiction-31160008 Middelgroot-911-09-032, Spinozapremie 56-464-14192); Center for Medical Systems Biology (CSMB, NWO Genomics); NBIC/BioAssist/RK(2008.024); Biobanking and Biomolecular Resources Research Infrastructure (BBMRI –NL, 184.021.007); The VU University’s Institute for Health and Care Research (EMGO+ ), Neuroscience Campus Amsterdam (NCA); The European Science Foundation: ESF, EU/QLRT-2001-01254; The European Science Council (ERC Advanced, 230374), Rutgers; University Cell and DNA Repository (NIMH U24 MH068457-06); The Avera Institute, Sioux Falls, South Dakota (USA); The National Institutes of Health: NIH, R01D0042157-01A; The Genetic Association Information Network (GAIN) of the Foundation for the US National Institutes of Health; NIMH: MH081802; The Chief Scientist Office of the Scottish Government: CZB/4/276 and CZB/4/710; The Royal Society; The MRC Human Genetics Unit; Arthritis Research UK and the European Union framework program 6 EUROSPAN project: LSHG-CT-2006-018947; AstraZeneca; The British Heart Foundation; The Oxford BHF Centre of Research Excellence; The Wellcome Trust: 075491/Z/04; The Swedish Research Council; The Knut and Alice Wallenberg Foundation; The Swedish Heart‐Lung Foundation; The Torsten and Ragnar Söderberg Foundation; The Strategic Cardiovascular Program of Karolinska Institutet and Stockholm County Council; The Foundation for Strategic Research and the Stockholm County Council: 560283; (PROMIS), The Wellcome Trust; (SardiNIA) The Intramural Research Program of the National Institute on Aging: NO1-AG-1–2109, 263-MA-410953; The National Institutes of Health: HG002651, HG005581, HL084729 The HUJ-CREATE Programme of the National Research Foundation, Singapore: 370062002; The U.S. National Institutes of Health: RO1CA55069, R35CA53890, R01CA80205 and R01CA144034 and UM1 CA182876; The Singapore National Medical Research Council: 1270/2010; The Fondo Europeo para el Desarrollo Regional: FEDER 2FD 1997/2309; Red de Centros RCMN: C03/08; Instituto de Salud Carlos III-RETIC RD06/0015/0012, Madrid, Spain, FIS 03/1618; CIBER in Diabetes and Associated Metabolic Disorders (ISCIII, Ministerio de Ciencia e Innovación) Madrid Autonomous Community: MOIR S2010/BMD-2423; Educational Grants from Eli Lilly Lab, Spain, Bayer Pharmaceutical Co.,Spain and Fundación Mutua Madrileña 2008, Spain. The Federal Ministry of Education and Research: 01ZZ9603, 01ZZ0103 and 01ZZ0403; The Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg - West Pomerania. The German Federal Ministry of Education and Research for "Zentren für Innovationskompetenz": ZIK; BMBF grant 03ZIK012; Siemens Healthcare, Erlangen, Germany and the Federal State of Mecklenburg- West Pomerania. The University of Greifswald is a member of the “Center of Knowledge Interchange“ program of the Siemens AG. The Sea Islands Genetics Network (SIGNET) was supported by R01 DK084350 and R01 DK084350 (MM Sale), and consists of data from the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort, (U01 NS041588; G Howard), Project SuGAR (Sea Islands Genetic African American Registry) (W.M. Keck Foundation; WT Garvey), a South Carolina Center of Biomedical Research Excellence (COBRE) in Oral Health Project P20 RR017696 (PI: Kirkwood; Sub-award: JK Fernandes), and the Systemic Lupus Erythematosus in Gullah Health (SLEIGH) study (PI: P60 AR049459, GS Gilkeson; K23 AR052364, DL Kamen; UL1 RR029882, KT Brady). The German Research Council (DFG - SFB 1052 “Obesity mechanisms”; A01, C01 and SPP 1629 TO 718/2-1); The German Diabetes Association and from the DHFD (Diabetes Hilfs- und Forschungsfonds Deutschland); The National Health Research Institutes, Taiwan (PH-100-SP-01, BS-094-PP-01, PH-100-PP-03); The National Science Council, Taiwan: NSC 98-2314-B-075A-002-MY3, NSC 96-2314-B-002-151, NSC 96-2314-B-002-152, NSC 98-2314-B-002-122-MY2, NSC 100-2314-B-002-115, NSC 101-2325-002-078, 101-2314-B-075A-006-MY3; The National Taiwan University Hospital, Taiwan: NTUH 98-N1266, NTUH 100-N1775, NTUH 101-N2010, NTUH 101-N, VN101-04, NTUH 101-S1784; The Netherlands Organization for Scientific Research NWO: GB-MW 940-38-011; ZonMW Brainpower: 100-001-004; ZonMw Risk Behavior and Dependence: 60-60600-97-118; ZonMw Culture and Health: 261-98-710; Social Sciences Council medium-sized investment grants: GB-MaGW 480-01-006 and GB-MaGW 480-07-001; Social Sciences Council project grants: GB-MaGW 452-04-314 and GB-MaGW 452-06-004; NWO large-sized investment grant: 175.010.2003.005; NWO Longitudinal Survey and Panel Funding: 481-08-013; The Dutch Ministry of Justice (WODC); The European Science Foundation (EuroSTRESS project FP-006); Biobanking and Biomolecular Resources Research Infrastructure BBMRI-NL (CP 32); The Netherlands Scientific Organization: NWO 480-05-003; The Dutch Brain Foundation; The US National Institutes of Health: AG028555, AG08724, AG04563, AG10175, AG08861; The Swedish Heart-Lung Foundation; The Swedish Foundation for Strategic Research; The Royal Swedish Academy of Science; The Ministry for Higher Education; The Swedish Research Council: M-2005-1112 and 2009-2298; GenomEUtwin (EU/QLRT-2001-01254; QLG2-CT-2002-01254); NIH grant DK U01-066134; Knut and Alice Wallenberg Foundation (Wallenberg Academy Fellow); European Research Council (ERC Starting Grant); Swedish Diabetes Foundation: 2013-024; Swedish Research Council: 2012-1397); Swedish Heart-Lung Foundation: 20120197; Uppsala University; Uppsala University Hospital; The Swedish Research Council for Infrastructures. Karolinska Institutet; Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) under Project b2011036. The Academia Sinica, Taipei, Taiwan, and Ministry of Science and Technology (Nation N); The National Heart, Lung, and Blood Institute: HL043851, HL080467; The National Cancer Institute: CA047988 and UM1CA182913; Amgen; The British Medical Research Council: MRC, K013351; The British Heart Foundation: PG/29605; The National Heart, Lung, and Blood Institute: R01HL036310en_US
dc.descriptionSource at: <a href=http://doi.org/10.1371/journal.pmed.1002383> http://doi.org/10.1371/journal.pmed.1002383 </a>en_US
dc.identifier.citationWheeler, E., Leong, A., Liu, C.-T., Hivert, M.-F., Strawbridge, R. J., Podmore, C., ... Meigs, J. B. (2017). Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis. PLoS Medicine. http://doi.org/10.1371/journal.pmed.1002383en_US
dc.identifier.cristinIDFRIDAID 1545183
dc.identifier.doi10.1371/journal.pmed.1002383
dc.identifier.issn1549-1277
dc.identifier.issn1549-1676
dc.identifier.urihttps://hdl.handle.net/10037/13158
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.journalPLoS Medicine
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/279153/EU/Beta-cell function in juvenile diabetes and obesity/BETA-JUDO/en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/279143/EU/Identification of epigenetic markers underlying increased risk of T2D in South Asians/EPI-MIGRANT/en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/201668/EU/European Collaborative Project on Inflamation and Vascular Wall Remodelling in Atherosclerosis/ATHEROREMO/en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/305739/EU/Personalized diagnostics and treatment of high risk coronary artery disease patients/RISKYCAD/en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/201681/EU/NOVEL PREP1-DEPENDENT TRANSCRIPTIONAL NETWORKS IN THE CONTROL OF INSULIN SENSITIVITY//en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/EU/FP7/257082/EU/Epigenetics towards systems biology/EPIGENESYS /en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/282510/EU/A BLUEPRINT of Haematopoietic Epigenomes/BLUEPRINT /en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/EU/FP7/201413/EU/European Network for Genetic and Genomic Epidemiology/ENGAGE/en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP6/37273/EU/A genome-wide mapping and functional genomics approach to elucidating precocious coronary artery disease/PROCARDIS/en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/EU/FP6/037197/EU/INTERACT//en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/FRIMED/185764/Norway/Diabetes and diabetes precursors: detection, classification, prediction, genetics, complications and prevention. The Tromsö Study//en_US
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Hematologi: 775en_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Hematology: 775en_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750en_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750en_US
dc.titleImpact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysisen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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