A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry

• Authors: KL Monda, University of North Carolina at Chapel Hill; GK Chen, University of Southern California; C Palmer, Broad Institute of Harvard & MIT; TL Edwards, Vanderbilt University; LA Lange, University of North Carolina; MCY Ng, Wake Forest University; AA Adeyemo, NHGRI; MA Allison, University of California San Diego; LF Bielak, University of Michigan; G Chen, NHGRI; M Graff, University of North Carolina; MR Irvin, University of Alabama Birmingham; SK Rhie, University of Southern California; G Li, University of Washington; Y Liu, Wake Forest University; Y Liu, University of North Carolina; Y Lu, Icahn School of Medicine at Mt Sinai; MA Nalls, NIA; Yan Sun, Emory University; MK Wojczynski, Washington University; LR Yanek, Johns Hopkins University; MC Aldrich, Vanderbilt University; A Ademola, Washington Univ; CI Amos, University of Texas MD Anderson Cancer Center; EV Bandera, Cancer Institute New Jersey; CH Bock, Wayne State University; A Britton, NIA; U Broeckel, Medical College of Wisconsin; Q Cai, Vanderbilt University; NE Caporaso, NCI; CS Carlson, Fred Hutchinson Cancer Research Center; J Carpten, Translational Genomics Research Institute; G Casey, University of Southern California; W-M Chen, University of Virginia; F Chen, University of Virginia; Y-DI Chen, Cedars Sinai Med Center; CWK Chiang, Harvard University; GA Coetzee, University of Southern California; E Demerath, University of Minnesota; SL Deming-Halverson, Vanderbilt University; RW Driver, American Cancer Society; P Dubbert, South Cent VA Mental Illness Res & Clin Ctr; MF Feitosa, Washington University; Y Feng, University of Southern California; BI Freedman, Wake Forest University; EM Gillanders, NCI; O Gottesman, Icahn Sch Med Mt Sinai; X Guo, Cedars Sinai Medical Center; T Haritunians, Cedars Sinai Medical Center; T Harris, NIA; CC Harris, NCI; AJM Hennis, SUNY Stony Brook; DG Hernandez, NIA; LH McNeill, University of Texas MD Anderson Cancer Center; TD Howard, Wake Forest University; BV Howard, MedStar Health Research Institute; VJ Howard, University of Alabama Birmingham; KC Johnson, University of Tennessee; SJ Kang, Suny Downstate Medical Center; BJ Keating, University of Pennsylvania; S Kolb, Fred Hutchinson Cancer Research Center; LH Kuller, University of Pittsburgh; A Kutlar, Georgia Health Sciences University; CD Langefeld, Wake Forest University; G Lettre, University of Montreal; K Lohman, Wake Forest University; V Lotay, Icahn School of Medicine at Mt Sinai; H Lyon, Harvard Medical School; JE Manson, Harvard University; W Maixner, University of North Carolina; YA Meng, Broad Institute of MIT and Harvard; KR Monroe, University of Southern California; I Morhason-Bello, Broad Institute of MIT and Harvard; AB Murphy, Northwestern University; JC Mychaleckyj, University of Virginia; R Nadukuru, Icahn School of Medicine at Mt Sinai; KL Nathanson, University of Pennsylvania; U Nayak, University of Virginia; A N'Diaye, Université de Montréal; B Nemesure, SUNY Stony Brook; S-Y Wu, SUNY Stony Brook; MC Leske, SUNY Stony Brook; C Neslund-Dudas, Henry Ford Hospital; M Neuhouser, Fred Hutchinson Cancer Research Center; S Nyante, University of North Carolina; H Ochs-Balcom, SUNY Buffalo; A Ogunniyi, University of Ibadan; TO Ogundiran, University of Ibadan; O Ojengbede, Broad Institute of MIT and Harvard; OI Olopade, University of Chicago; JR Palmer, Boston University; EA Ruiz-Narvaez, Boston University; ND Palmer, Wake Forest University; MF Press, University of Southern California; E Rampersaud, University of Miami; LJ Rasmussen-Torvik, Northwestern University; JL Rodriguez-Gil, University of Miami; B Salako, University of Ibadan; EE Schadt, Icahn School of Medicine at Mt Sinai; AG Schwartz, Wayne State University; DA Shriner, Wake Forest University; D Siscovick, University of Washington; SB Smith, University of North Carolina; S Wassertheil-Smoller, Albert Einstein College of Medicine; EK Speliotes, University of Michigan; MR Spitz, Baylor College of Medicine; L Sucheston, Roswell Park Cancer Institute; Herman Taylor, Emory University; BO Tayo, Loyola University Chicago; MA Tucker, NCI; DJ Van Den Berg, University of Southern California; DRV Edwards, Vanderbilt University; Z Wang, NCI; JK Wiencke, University of California San Francisco; TW Winkler, Icahn School of Medicine at Mt Sinai; JS Witte, University of California San Francisco; M Wrensch, University of California San Francisco; X Wu, University of Texas MD Anderson Cancer Center; JJ Yang, Henry Ford Hospital; AM Levin, Henry Ford Hospital; TR Young, Broad Institute of MIT and Harvard; NA Zakai, University of Vermont; M Cushman, University of Vermont; KA Zanetti, NCI; JH Zhao, Addenbrookes Hospital; W Zhao, University of Michigan; Y Zheng, University of Chicago; J Zhou, Wake Forest University; RG Ziegler, NCI; JM Zmuda, University of Pittsburgh; JK Fernandes, Medical University of South Carolina; GS Gilkeson, Medical University of South Carolina; DL Kamen, Medical University of South Carolina; KJ Hunt, Medical University of South Carolina; IJ Spruill, Medical University of South Carolina; CB Ambrosone, Roswell Park Cancer Institute; S Ambs, NCI; DK Arnett, University of Alabama Birmingham; L Atwood, Boston University; DM Becker, Johns Hopkins University; SI Berndt, NCI; L Bernstein, City Hope National Medical Center; WJ Blot, Vanderbilt University; IB Borecki, Washington University; EP Bottinger, Icahn School of Medicine at Mt Sinai; DW Bowden, Wake Forest University; Greg Burke, Emory University; SJ Chanock, NCI; RS Cooper, Loyola University Chicago; J Ding, Wake Forest University; D Duggan, Translational Genomics Research Institute; MK Evans, NIA; C Fox, NHLBI; WT Garvey, University of Alabama Birmingham; JP Bradfield, Childrens Hospital of Philadelphia; H Hakonarson, Childrens Hospital of Philadelphia; SFA Grant, Childrens Hospital of Philadelphia; A Hsing, Cancer Prevention Institute of California; L Chu, Stanford University; JJ Hu, University of Miami; D Huo, University of Chicago; SA Ingles, University of Southern California; EM John, Cancer Prevention Institute of California; JM Jordan, University of North Carolina; EK Kabagambe, Vanderbilt University; SLR Kardia, University of Michigan; RA Kittles, University of Chicago; PJ Goodman, SWOG Statistical Center; EA Klein, Cleveland Clinic; LN Kolonel, University of Hawaii; L Le Marchand, University of Hawaii; S Liu, University of California Los Angeles; B McKnight, University of Washington; RC Millikan, University of North Carolina; TH Mosley, University of Mississippi; B Padhukasahasram, Henry Ford Health System; LK Williams, Henry Ford Health System; SR Patel, Brigham & Womens Hospital; U Peters, Fred Hutchinson Cancer Research Center; CA Pettaway, University of Texas MD Anderson Cancer Center; PA Peyser, University of Michigan; BM Psaty, University of Washington; S Redline, Brigham & Womens Hospital; CN Rotimi, NHGRI; BA Rybicki, Henry Ford Hospital; MM Sale, University of Virginia; PJ Schreiner, University of Minnesota; LB Signorello, Harvard University; AB Singleton, NIA; JL Stanford, Fred Hutchinson Cancer Research Center; SS Strom, University of Texas MD Anderson Cancer Center; Michael Thun, Emory University; M Vitolins, Wake Forest University; W Zheng, Vanderbilt University; JH Moore, Dartmouth College; SM Williams, Dartmouth College; S Ketkar, NIA; X Zhu, NCI; AB Zonderman, NIA; C Kooperberg, Fred Hutchinson Cancer Research Center; GJ Papanicolaou, NHLBI; BE Henderson, University of Southern California; AP Reiner, Fred Hutchinson Cancer Research Center; JN Hirschhorn, Broad Institute of MIT and Harvard; RJF Loos, Icahn School of Medicine at Mt Sinai; KE North, University of North Carolina; CA Haiman, University of Southern California
• Journal Title: Nature Genetics
• Volume: Volume 45, Number 6
• Publisher: Nature Publishing Group | 2013-06-01, Pages 690-+
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1038/ng.2608
• Subjects: Biology, Genetics; Health Sciences, Nutrition; Health Sciences, Epidemiology; Health Sciences, Oncology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Genetics & Heredity; Genome-wide association; Multilocus genotype data; Common variants; Positive selection; Sequence variants; Human populations; Genetic variation; Adult obesity; FTO gene; Risk

Abstract

Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one new locus at 5q33 (GALNT10, rs7708584, P = 3.4 × 10-11) and another at 7p15 when we included data from the GIANT consortium (MIR148A-NFE2L3, rs10261878, P = 1.2 × 10-10). We also found suggestive evidence of an association at a third locus at 6q16 in the African-ancestry sample (KLHL32, rs974417, P = 6.9 × 10 -8). Thirty-two of the 36 previously established BMI variants showed directionally consistent effect estimates in our GWAS (binomial P = 9.7 × 10-7), five of which reached genome-wide significance. These findings provide strong support for shared BMI loci across populations, as well as for the utility of studying ancestrally diverse populations. © 2013 Nature America, Inc. All rights reserved.