A genome-wide association search for type 2 diabetes genes in african americans

DIAGRAM Consortium; MAGIC Investigators; Anders Hamsten on behalf of Procardis Consortium; DIAGRAM Consortium; GIANT Consortium; Global BPgen Consortium; for the MAGIC investigators

doi:10.1371/journal.pone.0029202

A genome-wide association search for type 2 diabetes genes in african americans

DIAGRAM Consortium
, MAGIC Investigators
, Anders Hamsten on behalf of Procardis Consortium
, DIAGRAM Consortium
, GIANT Consortium
, Global BPgen Consortium
, for the MAGIC investigators

Wake Forest University
Kaiser Permanente
University of Virginia
Howard University
Massachusetts Institute of Technology
Massachusetts General Hospital
Harvard University
Broad Institute
University of Michigan, Ann Arbor
deCODE Genetics
University of Oxford
CNRS
Institut Pasteur de Lille
Wellcome Trust Sanger Institute
Helmholtz Zentrum München - German Research Center for Environmental Health
Ludwig Maximilian University of Munich
Erasmus University Rotterdam
Ontario Institute for Cancer Research
University of Cambridge
University of Lübeck
Boston University
National Heart Lung and Blood Institute’s and Boston University’s Framingham Heart Study
NHS Lothian
University of Edinburgh
Vrije Universiteit Amsterdam
Institut national de la santé et de la recherche médicale
Université Paris-Saclay
Landspitali University Hospital
Icelandic Heart Association
Ulm University
University of Texas Health Science Center at Houston
National Institutes of Health
R&D Centre Skaraborg Primary Care
Catharina Hospital
Corbeil-Essonnes Hospital
Brigham and Women’s Hospital
University of North Carolina at Chapel Hill
University of Dundee
Novo Nordisk Foundation
CHU de Poitiers
German Diabetes Center Düsseldorf
Folkhalsan
Malmska Municipal Health Center and Hospital
Malmska Municipal Health Care Center and Hospital
University of Copenhagen
Johns Hopkins University
University of Eastern Finland
Aarhus University
Maxima Medical Centre
Lund University
Université Paris Cité
Technical University of Munich
Norwegian University of Science and Technology
Peninsula Medical School, Universities of Exeter and Plymouth
University of Exeter
Heinrich Heine University Düsseldorf
McGill University
Genome Quebec Innovation Centre
Norfolk and Norwich University Hospitals NHS Foundation Trust
Institut interrégional pour la Santé (IRSA)
Helsinki University Hospital
Utrecht University
University of Groningen
University of Southern California
Uppsala University
University of Southern Denmark
Queen Mary University of London
The Hospital of Levanger
EURAC Research
General Central Hospital
University of Split
National Institute for Health and Welfare
University of Helsinki
South Ostrobothnia Central Hospital
Newcastle University
University of Minnesota Twin Cities
University of Iceland
Hammersmith Hospital
National Institute for Health Research (NIHR) Oxford Biomedical Research Centre
St Thomas’ Hospital Campus
University of Washington
University of Lausanne
Imperial College London
Leiden University
GlaxoSmithKline
University of Oulu
NHS Tayside
Harokopio University
University College London
University of Bristol
Hospital Clínico San Carlos de Madrid
Karolinska Institutet
Washington University St. Louis
University of Maryland, Baltimore
Université de Lille
Heart Research Institute
PathWest Laboratory Medicine WA
University of Western Australia
Swiss Institute of Bioinformatics
Leipzig University
Cedars-Sinai Medical Center
National Research Council of Italy
Queen Elizabeth II Medical Centre Trust
Charité – Universitätsmedizin Berlin
German Institute of Human Nutrition Potsdam-Rehbruecke
IRCCS Istituto di ricerche farmacologiche Mario Negri - Milano, Bergamo, Ranica
Université Paris 13
Technische Universität Dresden
University of Texas Southwestern Medical Center
Umeå University
Centre National de Génotypage/Institut de génomique/Commissariat à l’énergie atomique
Centre de Recherche des Cordeliers
Sir Charles Gairdner Hospital
University of California at San Francisco
University of Ottawa
University of Campania Luigi Vanvitelli
University of Zagreb
VU University Medical Center
Group Health Cooperative
MRC Lifecourse Epidemiology Unit
University of Münster
Department of Veterans Affairs
MedStar Health
Université de Lorraine
Vrije Universiteit (VU)
University of Amsterdam
Queen's University Belfast
Swedish Medical Products Agency
London School of Hygiene and Tropical Medicine
Istituto Nazionale di Riposo e Cura per Anziani - Ancona

Research output: Contribution to journal › Article › peer-review

149 Citations (Scopus)

Abstract

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10^-8). SNP rs7560163 (P = 7.0×10^-9, OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10^-5) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.

Original language	English
Article number	e29202
Journal	PLoS ONE
Volume	7
Issue number	1
DOIs	https://doi.org/10.1371/journal.pone.0029202
Publication status	Published - 4 Jan 2012
Externally published	Yes

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@article{cd9ca240adc84e03a9580de3f7295a1b,

title = "A genome-wide association search for type 2 diabetes genes in african americans",

abstract = "African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10-8). SNP rs7560163 (P = 7.0×10-9, OR (95\% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10-5) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.",

author = "\{DIAGRAM Consortium\} and \{MAGIC Investigators\} and \{Anders Hamsten on behalf of Procardis Consortium\} and \{DIAGRAM Consortium\} and \{GIANT Consortium\} and \{Global BPgen Consortium\} and \{for the MAGIC investigators\} and Palmer, \{Nicholette D.\} and McDonough, \{Caitrin W.\} and Hicks, \{Pamela J.\} and Roh, \{Bong H.\} and Wing, \{Maria R.\} and An, \{S. Sandy\} and Hester, \{Jessica M.\} and Cooke, \{Jessica N.\} and Bostrom, \{Meredith A.\} and Rudock, \{Megan E.\} and Talbert, \{Matthew E.\} and Lewis, \{Joshua P.\} and Assiamira Ferrara and Lingyi Lu and Ziegler, \{Julie T.\} and Sale, \{Michele M.\} and Jasmin Divers and Daniel Shriner and Adebowale Adeyemo and Rotimi, \{Charles N.\} and Ng, \{Maggie C.Y.\} and Langefeld, \{Carl D.\} and Freedman, \{Barry I.\} and Bowden, \{Donald W.\} and Voight, \{Benjamin F.\} and Scott, \{Laura J.\} and Valgerdur Steinthorsdottir and Morris, \{Andrew P.\} and Christian Dina and Welch, \{Ryan P.\} and Eleftheria Zeggini and Cornelia Huth and Aulchenko, \{Yurii S.\} and Gudmar Thorleifs-Son and McCulloch, \{Laura J.\} and Teresa Ferreira and Harald Grallert and Najaf Amin and Guanming Wu and Willer, \{Cristen J.\} and Soumya Raychaudhuri and McCarroll, \{Steven A.\} and Claudia Langenberg and Hofmann, \{Oliver M.\} and Jos{\'e}e Dupuis and Lu Qi and Segr{\`e}, \{Ayellet V.\} and \{van Hoek\}, Mandy and Pau Navarro and Hottenga, \{Jouke Jan\}",

year = "2012",

month = jan,

day = "4",

doi = "10.1371/journal.pone.0029202",

language = "English",

volume = "7",

journal = "PLoS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "1",

}

TY - JOUR

T1 - A genome-wide association search for type 2 diabetes genes in african americans

AU - DIAGRAM Consortium

AU - MAGIC Investigators

AU - Anders Hamsten on behalf of Procardis Consortium

AU - DIAGRAM Consortium

AU - GIANT Consortium

AU - Global BPgen Consortium

AU - for the MAGIC investigators

AU - Palmer, Nicholette D.

AU - McDonough, Caitrin W.

AU - Hicks, Pamela J.

AU - Roh, Bong H.

AU - Wing, Maria R.

AU - An, S. Sandy

AU - Hester, Jessica M.

AU - Cooke, Jessica N.

AU - Bostrom, Meredith A.

AU - Rudock, Megan E.

AU - Talbert, Matthew E.

AU - Lewis, Joshua P.

AU - Ferrara, Assiamira

AU - Lu, Lingyi

AU - Ziegler, Julie T.

AU - Sale, Michele M.

AU - Divers, Jasmin

AU - Shriner, Daniel

AU - Adeyemo, Adebowale

AU - Rotimi, Charles N.

AU - Ng, Maggie C.Y.

AU - Langefeld, Carl D.

AU - Freedman, Barry I.

AU - Bowden, Donald W.

AU - Voight, Benjamin F.

AU - Scott, Laura J.

AU - Steinthorsdottir, Valgerdur

AU - Morris, Andrew P.

AU - Dina, Christian

AU - Welch, Ryan P.

AU - Zeggini, Eleftheria

AU - Huth, Cornelia

AU - Aulchenko, Yurii S.

AU - Thorleifs-Son, Gudmar

AU - McCulloch, Laura J.

AU - Ferreira, Teresa

AU - Grallert, Harald

AU - Amin, Najaf

AU - Wu, Guanming

AU - Willer, Cristen J.

AU - Raychaudhuri, Soumya

AU - McCarroll, Steven A.

AU - Langenberg, Claudia

AU - Hofmann, Oliver M.

AU - Dupuis, Josée

AU - Qi, Lu

AU - Segrè, Ayellet V.

AU - van Hoek, Mandy

AU - Navarro, Pau

AU - Hottenga, Jouke Jan

PY - 2012/1/4

Y1 - 2012/1/4

N2 - African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10-8). SNP rs7560163 (P = 7.0×10-9, OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10-5) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.

AB - African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10-8). SNP rs7560163 (P = 7.0×10-9, OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10-5) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.

UR - https://www.scopus.com/pages/publications/84855405312

U2 - 10.1371/journal.pone.0029202

DO - 10.1371/journal.pone.0029202

M3 - Article

C2 - 22238593

AN - SCOPUS:84855405312

SN - 1932-6203

VL - 7

JO - PLoS ONE

JF - PLoS ONE

IS - 1

M1 - e29202

ER -

A genome-wide association search for type 2 diabetes genes in african americans

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