Genome-wide association of body fat distribution in African ancestry populations suggests new loci.

PLoS Genetics. 2013;9(8):e1003681 DOI 10.1371/journal.pgen.1003681

 

Journal Homepage

Journal Title: PLoS Genetics

ISSN: 1553-7390 (Print); 1553-7404 (Online)

Publisher: Public Library of Science (PLoS)

LCC Subject Category: Science: Biology (General): Genetics

Country of publisher: United States

Language of fulltext: English

Full-text formats available: PDF, HTML, XML

 

AUTHORS


Ching-Ti Liu

Keri L Monda

Kira C Taylor

Leslie Lange

Ellen W Demerath

Walter Palmas

Mary K Wojczynski

Jaclyn C Ellis

Mara Z Vitolins

Simin Liu

George J Papanicolaou

Marguerite R Irvin

Luting Xue

Paula J Griffin

Michael A Nalls

Adebowale Adeyemo

Jiankang Liu

Guo Li

Edward A Ruiz-Narvaez

Wei-Min Chen

Fang Chen

Brian E Henderson

Robert C Millikan

Christine B Ambrosone

Sara S Strom

Xiuqing Guo

Jeanette S Andrews

Yan V Sun

Thomas H Mosley

Lisa R Yanek

Daniel Shriner

Talin Haritunians

Jerome I Rotter

Elizabeth K Speliotes

Megan Smith

Lynn Rosenberg

Josyf Mychaleckyj

Uma Nayak

Ida Spruill

W Timothy Garvey

Curtis Pettaway

Sarah Nyante

Elisa V Bandera

Angela F Britton

Alan B Zonderman

Laura J Rasmussen-Torvik

Yii-Der Ida Chen

Jingzhong Ding

Kurt Lohman

Stephen B Kritchevsky

Wei Zhao

Patricia A Peyser

Sharon L R Kardia

Edmond Kabagambe

Ulrich Broeckel

Guanjie Chen

Jie Zhou

Sylvia Wassertheil-Smoller

Marian L Neuhouser

Evadnie Rampersaud

Bruce Psaty

Charles Kooperberg

Joann E Manson

Lewis H Kuller

Heather M Ochs-Balcom

Karen C Johnson

Lara Sucheston

Jose M Ordovas

Julie R Palmer

Christopher A Haiman

Barbara McKnight

Barbara V Howard

Diane M Becker

Lawrence F Bielak

Yongmei Liu

Matthew A Allison

Struan F A Grant

Gregory L Burke

Sanjay R Patel

Pamela J Schreiner

Ingrid B Borecki

Michele K Evans

Herman Taylor

Michele M Sale

Virginia Howard

Christopher S Carlson

Charles N Rotimi

Mary Cushman

Tamara B Harris

Alexander P Reiner

L Adrienne Cupples

Kari E North

Caroline S Fox

EDITORIAL INFORMATION

Peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 26 weeks

 

Abstract | Full Text

Central obesity, measured by waist circumference (WC) or waist-hip ratio (WHR), is a marker of body fat distribution. Although obesity disproportionately affects minority populations, few studies have conducted genome-wide association study (GWAS) of fat distribution among those of predominantly African ancestry (AA). We performed GWAS of WC and WHR, adjusted and unadjusted for BMI, in up to 33,591 and 27,350 AA individuals, respectively. We identified loci associated with fat distribution in AA individuals using meta-analyses of GWA results for WC and WHR (stage 1). Overall, 25 SNPs with single genomic control (GC)-corrected p-values<5.0 × 10(-6) were followed-up (stage 2) in AA with WC and with WHR. Additionally, we interrogated genomic regions of previously identified European ancestry (EA) WHR loci among AA. In joint analysis of association results including both Stage 1 and 2 cohorts, 2 SNPs demonstrated association, rs2075064 at LHX2, p = 2.24×10(-8) for WC-adjusted-for-BMI, and rs6931262 at RREB1, p = 2.48×10(-8) for WHR-adjusted-for-BMI. However, neither signal was genome-wide significant after double GC-correction (LHX2: p = 6.5 × 10(-8); RREB1: p = 5.7 × 10(-8)). Six of fourteen previously reported loci for waist in EA populations were significant (p<0.05 divided by the number of independent SNPs within the region) in AA studied here (TBX15-WARS2, GRB14, ADAMTS9, LY86, RSPO3, ITPR2-SSPN). Further, we observed associations with metabolic traits: rs13389219 at GRB14 associated with HDL-cholesterol, triglycerides, and fasting insulin, and rs13060013 at ADAMTS9 with HDL-cholesterol and fasting insulin. Finally, we observed nominal evidence for sexual dimorphism, with stronger results in AA women at the GRB14 locus (p for interaction = 0.02). In conclusion, we identified two suggestive loci associated with fat distribution in AA populations in addition to confirming 6 loci previously identified in populations of EA. These findings reinforce the concept that there are fat distribution loci that are independent of generalized adiposity.