Meta-Analysis of Genome-Wide Association Studies in African Americans Provides Insights into the Genetic Architecture of Type 2 Diabetes

Maggie C. Y. Ng; Daniel Shriner; Brian H. Chen; Jiang Li; Wei-Min Chen; Xiuqing Guo; Jiankang Liu; Suzette J. Bielinski; Lisa R. Yanek; Michael A. Nalls; Mary E. Comeau; Laura J. Rasmussen-Torvik; Richard A. Jensen; Daniel S. Evans; Yan V. Sun; Ping An; Sanjay R. Patel; Yingchang Lu; Jirong Long; Loren L. Armstrong; Lynne Wagenknecht; Lingyao Yang; Beverly M. Snively; Nicholette D. Palmer; Poorva Mudgal; Carl D. Langefeld; Keith L. Keene; Barry I. Freedman; Josyf C. Mychaleckyj; Uma Nayak; Leslie J. Raffel; Mark O. Goodarzi; Y-D Ida Chen; Herman A. Taylor; Adolfo Correa; Mario Sims; David Couper; James S. Pankow; Eric Boerwinkle; Adebowale Adeyemo; Ayo Doumatey; Guanjie Chen; Rasika A. Mathias; Dhananjay Vaidya; Andrew B. Singleton; Alan B. Zonderman; Robert P. Igo; John R. Sedor; Edmond K. Kabagambe; David S. Siscovick; Barbara McKnight; Kenneth Rice; Yongmei Liu; Wen-Chi Hsueh; Wei Zhao; Lawrence F. Bielak; Aldi Kraja; Michael A. Province; Erwin P. Bottinger; Omri Gottesman; Qiuyin Cai; Wei Zheng; William J. Blot; William L. Lowe; Jennifer A. Pacheco; Dana C. Crawford; Elin Grundberg; Stephen S. Rich; M. Geoffrey Hayes; Xiao-Ou Shu; Ruth J. F. Loos; Ingrid B. Borecki; Patricia A. Peyser; Steven R. Cummings; Bruce M. Psaty; Myriam Fornage; Sudha K. Iyengar; Michele K. Evans; Diane M. Becker; W. H. Linda Kao; James G. Wilson; Jerome I. Rotter; Michele M. Sale; Simin Liu; Charles N. Rotimi; Donald W. Bowden; FIND Consortium; Inga Prokopenko

doi:10.1371/journal.pgen.1004517

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Meta-Analysis of Genome-Wide Association Studies in African Americans Provides Insights into the Genetic Architecture of Type 2 Diabetes

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Meta-Analysis of Genome-Wide Association Studies in African Americans Provides Insights into the Genetic Architecture of Type 2 Diabetes

Maggie C. Y. Ng, Daniel Shriner, Brian H. Chen, Jiang Li, Wei-Min Chen, Xiuqing Guo, Jiankang Liu, Suzette J. Bielinski, Lisa R. Yanek, Michael A. Nalls, …

PLoS genetics, Vol.10(8), p.e1004517

01/08/2014

DOI: https://doi.org/10.1371/journal.pgen.1004517

PMID: 25102180

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15x10(-94) < P < 5x10(-8), odds ratio (OR) = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2x10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.

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Title: Meta-Analysis of Genome-Wide Association Studies in African Americans Provides Insights into the Genetic Architecture of Type 2 Diabetes
Creators: Maggie C. Y. Ng - Supreme Council Of Health
Daniel Shriner - National Human Genome Research Institute
Brian H. Chen - University of California, Los Angeles
Jiang Li - Supreme Council Of Health
Wei-Min Chen - University of Virginia
Xiuqing Guo - The Lundquist Institute
Jiankang Liu - University of Mississippi Medical Center
Suzette J. Bielinski - Mayo Clinic in Florida
Lisa R. Yanek - Johns Hopkins University
Michael A. Nalls - National Institute on Aging
Mary E. Comeau - North Carolina Division of Public Health
Laura J. Rasmussen-Torvik - Northwestern University
Richard A. Jensen - University of Washington
Daniel S. Evans - California Pacific Medical Center
Yan V. Sun - Emory University
Ping An - Washington University in St. Louis
Sanjay R. Patel - Brigham and Women's Hospital
Yingchang Lu - Icahn School of Medicine at Mount Sinai
Jirong Long - Vanderbilt University
Loren L. Armstrong - Northwestern University
Lynne Wagenknecht - Wake Forest University
Lingyao Yang - Wake Forest University
Beverly M. Snively - Wake Forest University
Nicholette D. Palmer - Wake Forest University
Poorva Mudgal - Wake Forest University
Carl D. Langefeld - North Carolina Division of Public Health
Keith L. Keene - East Carolina University
Barry I. Freedman - Wake Forest University
Josyf C. Mychaleckyj - University of Virginia
Uma Nayak - University of Virginia
Leslie J. Raffel - Cedars-Sinai Medical Center
Mark O. Goodarzi - Cedars-Sinai Medical Center
Y-D Ida Chen - The Lundquist Institute
Herman A. Taylor - Tougaloo College
Adolfo Correa - University of Mississippi Medical Center
Mario Sims - University of Mississippi Medical Center
David Couper - University of North Carolina at Chapel Hill
James S. Pankow - University of Minnesota
Eric Boerwinkle - The University of Texas Health Science Center at Houston
Adebowale Adeyemo - National Human Genome Research Institute
Ayo Doumatey - National Human Genome Research Institute
Guanjie Chen - National Human Genome Research Institute
Rasika A. Mathias - Johns Hopkins Medicine
Dhananjay Vaidya - Johns Hopkins Medicine
Andrew B. Singleton - National Institute on Aging
Alan B. Zonderman - National Institute on Aging
Robert P. Igo - Case Western Reserve University
John R. Sedor - Case Western Reserve University
Edmond K. Kabagambe - Vanderbilt University Medical Center
David S. Siscovick - University of Washington
Barbara McKnight - University of Washington
Kenneth Rice - University of Washington
Yongmei Liu - Wake Forest University
Wen-Chi Hsueh - University of California, San Francisco
Wei Zhao - Michigan United
Lawrence F. Bielak - University of Michigan–Ann Arbor
Aldi Kraja - Washington University in St. Louis
Michael A. Province - Washington University in St. Louis
Erwin P. Bottinger - Icahn School of Medicine at Mount Sinai
Omri Gottesman - Icahn School of Medicine at Mount Sinai
Qiuyin Cai - Vanderbilt University
Wei Zheng - Vanderbilt University
William J. Blot - Vanderbilt University
William L. Lowe - Northwestern University
Jennifer A. Pacheco - Northwestern University
Dana C. Crawford - Center for Human Genetics
Elin Grundberg - King's College London
Stephen S. Rich - University of Virginia
M. Geoffrey Hayes - Northwestern University
Xiao-Ou Shu - Vanderbilt University
Ruth J. F. Loos - Icahn School of Medicine at Mount Sinai
Ingrid B. Borecki - Washington University in St. Louis
Patricia A. Peyser - University of Michigan–Ann Arbor
Steven R. Cummings - California Pacific Medical Center
Bruce M. Psaty - University of Washington
Myriam Fornage - The University of Texas Health Science Center at Houston
Sudha K. Iyengar - Case Western Reserve University
Michele K. Evans - National Institutes of Health
Diane M. Becker - Johns Hopkins University
W. H. Linda Kao - Johns Hopkins University
James G. Wilson - University of Mississippi Medical Center
Jerome I. Rotter - The Lundquist Institute
Michele M. Sale - University of Virginia
Simin Liu - Brown University
Charles N. Rotimi - National Human Genome Research Institute
Donald W. Bowden - Wake Forest University
FIND Consortium
Inga Prokopenko - School of Biosciences
Publication Details: PLoS genetics, Vol.10(8), p.e1004517
Publisher: Public Library Science
Number of pages: 14
Date published: 01/08/2014
Grant note: RD831697 / US EPA -Science to Achieve Results (STAR) Program MC_UU_12015/1 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) M01-RR-07122 / Wake Forest University HL087660; HL100245; HL100185 / National Institutes of Health from the National Heart, Lung, and Blood Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) NR0224103 / National Institute of Nursing Research; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Nursing Research (NINR) Z01-AG000513; 2009-149 / National Center on Minority Health and Health Disparities; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Minority Health & Health Disparities (NIMHD) U01-HG-004610; U01-HG-004608; U01-HG-04599; U01HG004609; U01-HG-04603 / NIGMS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) UL1TR000124 / National Center for Advancing Translational Sciences Grant HSC M01-RR-00997 / University of New Mexico HL62985 / National Heart, Lung, and Blood Institute, Bethesda, MD; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
Identifiers: 99928900302346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

Meta-Analysis of Genome-Wide Association Studies in African Americans Provides Insights into the Genetic Architecture of Type 2 Diabetes

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