Genome-Wide Association of Body Fat Distribution in African Ancestry Populations Suggests New Loci
Creators: name: Liu, Ching-Ti
name: Monda, Keri L.
name: Taylor, Kira C.
name: Lange, Leslie
name: Demerath, Ellen W.
name: Palmas, Walter R.
name: Wojczynski, Mary K.
name: Ellis, Jaclyn C.
name: Vitolins, Mara Z.
name: Liu, Simin
name: Papanicolaou, George J.
name: Irvin, Marguerite R.
name: Xue, Luting
name: Griffin, Paula J.
name: Nalls, Michael A.
name: Adeyemo, Adebowale
name: Liu, Jiankang
name: Li, Guo
name: Ruiz-Narvaez, Edward A.
name: Chen, Wei-Min
name: Chen, Fang
name: Henderson, Brian E.
name: Millikan, Robert C.
name: Ambrosone, Christine B.
name: Strom, Sara S.
name: Guo, Xiuqing
name: Andrews, Jeanette S.
name: Sun, Yan V.
name: Mosley, Thomas H.
name: Yanek, Lisa R.
name: Shriner, Daniel
name: Haritunians, Talin
name: Rotter, Jerome I.
name: Speliotes, Elizabeth K.
name: Smith, Megan
name: Rosenberg, Lynn
name: Mychaleckyj, Josyf
name: Nayak, Uma
name: Spruill, Ida
name: Garvey, W. Timothy
name: Pettaway, Curtis
name: Nyante, Sarah
name: Bandera, Elisa V.
name: Britton, Angela F.
name: Zonderman, Alan B.
name: Rasmussen-Torvik, Laura J.
name: Chen, Yii-Der Ida
name: Ding, Jingzhong
name: Lohman, Kurt
name: Kritchevsky, Stephen B.
name: Zhao, Wei
name: Peyser, Patricia A.
name: Kardia, Sharon L. R.
name: Kabagambe, Edmond
name: Broeckel, Ulrich
name: Chen, Guanjie
name: Zhou, Jie
name: Wassertheil-Smoller, Sylvia
name: Neuhouser, Marian L.
name: Rampersaud, Evadnie
name: Psaty, Bruce
name: Kooperberg, Charles
name: Manson, JoAnn E.
name: Kuller, Lewis H.
name: Ochs-Balcom, Heather M.
name: Johnson, Karen C.
name: Sucheston, Lara
name: Ordovas, Jose M.
name: Palmer, Julie R.
name: Haiman, Christopher A.
name: McKnight, Barbara
name: Howard, Barbara V.
name: Becker, Diane M.
name: Bielak, Lawrence F.
name: Liu, Yongmei
name: Allison, Matthew A.
name: Grant, Struan F. A.
name: Burke, Gregory L.
name: Patel, Sanjay R.
name: Schreiner, Pamela J.
name: Borecki, Ingrid B.
name: Evans, Michele K.
name: Taylor, Herman
name: Sale, Michele M.
name: Howard, Virginia
name: Carlson, Christopher S.
name: Rotimi, Charles N.
name: Cushman, Mary
name: Harris, Tamara B.
name: Reiner, Alexander P.
name: Cupples, L. Adrienne
name: North, Kari E.
name: Fox, Caroline S.
Publisher: name: Columbia University
Year: 2013
Subjects: subject: Obesity--Genetic aspects
subject: African Americans--Health and hygiene
subject: Gene mapping
subject: Genomics
subject: Genetics
subject: FOS: Biological sciences
subject: Molecular biology
subject: Epidemiology

description: 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&lt;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&lt;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.