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@article{Wheeler:2017:10.1371/journal.pmed.1002383,
author = {Wheeler, E and Leong, A and Liu, C-T and Hivert, M-F and Strawbridge, RJ and Podmore, C and Li, M and Yao, J and Sim, X and Hong, J and Chu, AY and Zhang, W and Wang, X and Chen, P and Maruthur, NM and Porneala, BC and Sharp, SJ and Jia, Y and Kabagambe, EK and Chang, L-C and Chen, W-M and Elks, CE and Evans, DS and Fan, Q and Giulianini, F and Go, MJ and Hottenga, J-J and Hu, Y and Jackson, AU and Kanoni, S and Kim, YJ and Kleber, ME and Ladenvall, C and Lecoeur, C and Lim, S-H and Lu, Y and Mahajan, A and Marzi, C and Nalls, MA and Navarro, P and Nolte, IM and Rose, LM and Rybin, DV and Sanna, S and Shi, Y and Stram, DO and Takeuchi, F and Tan, SP and van, der Most PJ and Van, Vliet-Ostaptchouk JV and Wong, A and Yengo, L and Zhao, W and Goel, A and Martinez, Larrad MT and Radke, D and Salo, P and Tanaka, T and van, Iperen EPA and Abecasis, G and Afaq, S and Alizadeh, BZ and Bertoni, AG and Bonnefond, A and Böttcher, Y and Bottinger, EP and Campbell, H and Carlson, OD and Chen, C-H a},
doi = {10.1371/journal.pmed.1002383},
journal = {PLoS Medicine},
title = {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.},
url = {http://dx.doi.org/10.1371/journal.pmed.1002383},
volume = {14},
year = {2017}
}

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TY  - JOUR
AB  - BACKGROUND: 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. METHODS & FINDINGS: 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
AU  - Wheeler,E
AU  - Leong,A
AU  - Liu,C-T
AU  - Hivert,M-F
AU  - Strawbridge,RJ
AU  - Podmore,C
AU  - Li,M
AU  - Yao,J
AU  - Sim,X
AU  - Hong,J
AU  - Chu,AY
AU  - Zhang,W
AU  - Wang,X
AU  - Chen,P
AU  - Maruthur,NM
AU  - Porneala,BC
AU  - Sharp,SJ
AU  - Jia,Y
AU  - Kabagambe,EK
AU  - Chang,L-C
AU  - Chen,W-M
AU  - Elks,CE
AU  - Evans,DS
AU  - Fan,Q
AU  - Giulianini,F
AU  - Go,MJ
AU  - Hottenga,J-J
AU  - Hu,Y
AU  - Jackson,AU
AU  - Kanoni,S
AU  - Kim,YJ
AU  - Kleber,ME
AU  - Ladenvall,C
AU  - Lecoeur,C
AU  - Lim,S-H
AU  - Lu,Y
AU  - Mahajan,A
AU  - Marzi,C
AU  - Nalls,MA
AU  - Navarro,P
AU  - Nolte,IM
AU  - Rose,LM
AU  - Rybin,DV
AU  - Sanna,S
AU  - Shi,Y
AU  - Stram,DO
AU  - Takeuchi,F
AU  - Tan,SP
AU  - van,der Most PJ
AU  - Van,Vliet-Ostaptchouk JV
AU  - Wong,A
AU  - Yengo,L
AU  - Zhao,W
AU  - Goel,A
AU  - Martinez,Larrad MT
AU  - Radke,D
AU  - Salo,P
AU  - Tanaka,T
AU  - van,Iperen EPA
AU  - Abecasis,G
AU  - Afaq,S
AU  - Alizadeh,BZ
AU  - Bertoni,AG
AU  - Bonnefond,A
AU  - Böttcher,Y
AU  - Bottinger,EP
AU  - Campbell,H
AU  - Carlson,OD
AU  - Chen,C-H
AU  - Cho,YS
AU  - Garvey,WT
AU  - Gieger,C
AU  - Goodarzi,MO
AU  - Grallert,H
AU  - Hamsten,A
AU  - Hartman,CA
AU  - Herder,C
AU  - Hsiung,CA
AU  - Huang,J
AU  - Igase,M
AU  - Isono,M
AU  - Katsuya,T
AU  - Khor,C-C
AU  - Kiess,W
AU  - Kohara,K
AU  - Kovacs,P
AU  - Lee,J
AU  - Lee,W-J
AU  - Lehne,B
AU  - Li,H
AU  - Liu,J
AU  - Lobbens,S
AU  - Luan,J
AU  - Lyssenko,V
AU  - Meitinger,T
AU  - Miki,T
AU  - Miljkovic,I
AU  - Moon,S
AU  - Mulas,A
AU  - Müller,G
AU  - Müller-Nurasyid,M
AU  - Nagaraja,R
AU  - Nauck,M
AU  - Pankow,JS
AU  - Polasek,O
AU  - Prokopenko,I
AU  - Ramos,PS
AU  - Rasmussen-Torvik,L
AU  - Rathmann,W
AU  - Rich,SS
AU  - Robertson,NR
AU  - Roden,M
AU  - Roussel,R
AU  - Rudan,I
AU  - Scott,RA
AU  - Scott,WR
AU  - Sennblad,B
AU  - Siscovick,DS
AU  - Strauch,K
AU  - Sun,L
AU  - Swertz,M
AU  - Tajuddin,SM
AU  - Taylor,KD
AU  - Teo,Y-Y
AU  - Tham,YC
AU  - Tönjes,A
AU  - Wareham,NJ
AU  - Willemsen,G
AU  - Wilsgaard,T
AU  - Hingorani,AD
AU  - EPIC-CVD,Consortium
AU  - EPIC-InterAct,Consortium
AU  - Lifelines,Cohort Study
AU  - Egan,J
AU  - Ferrucci,L
AU  - Hovingh,GK
AU  - Jula,A
AU  - Kivimaki,M
AU  - Kumari,M
AU  - Njølstad,I
AU  - Palmer,CNA
AU  - Serrano,Ríos M
AU  - Stumvoll,M
AU  - Watkins,H
AU  - Aung,T
AU  - Blüher,M
AU  - Boehnke,M
AU  - Boomsma,DI
AU  - Bornstein,SR
AU  - Chambers,JC
AU  - Chasman,DI
AU  - Chen,Y-DI
AU  - Chen,Y-T
AU  - Cheng,C-Y
AU  - Cucca,F
AU  - de,Geus EJC
AU  - Deloukas,P
AU  - Evans,MK
AU  - Fornage,M
AU  - Friedlander,Y
AU  - Froguel,P
AU  - Groop,L
AU  - Gross,MD
AU  - Harris,TB
AU  - Hayward,C
AU  - Heng,C-K
AU  - Ingelsson,E
AU  - Kato,N
AU  - Kim,B-J
AU  - Koh,W-P
AU  - Kooner,JS
AU  - Körner,A
AU  - Kuh,D
AU  - Kuusisto,J
AU  - Laakso,M
AU  - Lin,X
AU  - Liu,Y
AU  - Loos,RJF
AU  - Magnusson,PKE
AU  - März,W
AU  - McCarthy,MI
AU  - Oldehinkel,AJ
AU  - Ong,KK
AU  - Peder
DO  - 10.1371/journal.pmed.1002383
PY  - 2017///
SN  - 1549-1277
TI  - 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.
T2  - PLoS Medicine
UR  - http://dx.doi.org/10.1371/journal.pmed.1002383
UR  - http://hdl.handle.net/10044/1/50650
VL  - 14
ER  -

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