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


ABSTRACT: 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.

SUBMITTER: Liu CT 

PROVIDER: S-EPMC3744443 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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

Liu Ching-Ti CT   Monda Keri L KL   Taylor Kira C KC   Lange Leslie L   Demerath Ellen W EW   Palmas Walter W   Wojczynski Mary K MK   Ellis Jaclyn C JC   Vitolins Mara Z MZ   Liu Simin S   Papanicolaou George J GJ   Irvin Marguerite R MR   Xue Luting L   Griffin Paula J PJ   Nalls Michael A MA   Adeyemo Adebowale A   Liu Jiankang J   Li Guo G   Ruiz-Narvaez Edward A EA   Chen Wei-Min WM   Chen Fang F   Henderson Brian E BE   Millikan Robert C RC   Ambrosone Christine B CB   Strom Sara S SS   Guo Xiuqing X   Andrews Jeanette S JS   Sun Yan V YV   Mosley Thomas H TH   Yanek Lisa R LR   Shriner Daniel D   Haritunians Talin T   Rotter Jerome I JI   Speliotes Elizabeth K EK   Smith Megan M   Rosenberg Lynn L   Mychaleckyj Josyf J   Nayak Uma U   Spruill Ida I   Garvey W Timothy WT   Pettaway Curtis C   Nyante Sarah S   Bandera Elisa V EV   Britton Angela F AF   Zonderman Alan B AB   Rasmussen-Torvik Laura J LJ   Chen Yii-Der Ida YD   Ding Jingzhong J   Lohman Kurt K   Kritchevsky Stephen B SB   Zhao Wei W   Peyser Patricia A PA   Kardia Sharon L R SL   Kabagambe Edmond E   Broeckel Ulrich U   Chen Guanjie G   Zhou Jie J   Wassertheil-Smoller Sylvia S   Neuhouser Marian L ML   Rampersaud Evadnie E   Psaty Bruce B   Kooperberg Charles C   Manson Joann E JE   Kuller Lewis H LH   Ochs-Balcom Heather M HM   Johnson Karen C KC   Sucheston Lara L   Ordovas Jose M JM   Palmer Julie R JR   Haiman Christopher A CA   McKnight Barbara B   Howard Barbara V BV   Becker Diane M DM   Bielak Lawrence F LF   Liu Yongmei Y   Allison Matthew A MA   Grant Struan F A SF   Burke Gregory L GL   Patel Sanjay R SR   Schreiner Pamela J PJ   Borecki Ingrid B IB   Evans Michele K MK   Taylor Herman H   Sale Michele M MM   Howard Virginia V   Carlson Christopher S CS   Rotimi Charles N CN   Cushman Mary M   Harris Tamara B TB   Reiner Alexander P AP   Cupples L Adrienne LA   North Kari E KE   Fox Caroline S CS  

PLoS genetics 20130815 8


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  ...[more]

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