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


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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



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


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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.