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

MedStar author(s):
Citation: PLoS Genetics. 9(8):e1003681, 2013.PMID: 23966867Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Journal Article | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov't | Research Support, U.S. Gov't, Non-P.H.S.Subject headings: *African Continental Ancestry Group/ge [Genetics] | *Body Fat Distribution | *Genome-Wide Association Study | *Obesity/ge [Genetics] | Adiposity/ge [Genetics] | European Continental Ancestry Group/ge [Genetics] | Female | Genetic Loci | Humans | Male | Obesity/pa [Pathology] | Polymorphism, Single Nucleotide | Waist-Hip RatioLocal holdings: Available online through MWHC library: 2005 - presentISSN:
  • 1553-7390
Name of journal: PLoS geneticsAbstract: 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 x 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 = 2.24x10(-8) for WC-adjusted-for-BMI, and rs6931262 at RREB1, p = 2.48x10(-8) for WHR-adjusted-for-BMI. However, neither signal was genome-wide significant after double GC-correction (LHX2: p = 6.5 x 10(-8); RREB1: p = 5.7 x 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.All authors: Adeyemo A, Allison MA, Ambrosone CB, Andrews JS, Bandera EV, Becker DM, Bielak LF, Borecki IB, Britton AF, Broeckel U, Burke GL, Carlson CS, Chen F, Chen G, Chen WM, Chen YD, Cupples LA, Cushman M, Demerath EW, Ding J, Ellis JC, Evans MK, Fox CS, Garvey WT, Grant SF, Griffin PJ, Guo X, Haiman CA, Haritunians T, Harris TB, Henderson BE, Howard BV, Howard V, Irvin MR, Johnson KC, Kabagambe E, Kardia SL, Kooperberg C, Kritchevsky SB, Kuller LH, Lange L, Li G, Liu CT, Liu J, Liu S, Liu Y, Lohman K, Manson JE, McKnight B, Millikan RC, Monda KL, Mosley TH, Mychaleckyj J, Nalls MA, Nayak U, Neuhouser ML, North KE, Nyante S, Ochs-Balcom HM, Ordovas JM, Palmas W, Palmer JR, Papanicolaou GJ, Patel SR, Pettaway C, Peyser PA, Psaty B, Rampersaud E, Rasmussen-Torvik LJ, Reiner AP, Rosenberg L, Rotimi CN, Rotter JI, Ruiz-Narvaez EA, Sale MM, Schreiner PJ, Shriner D, Smith M, Speliotes EK, Spruill I, Strom SS, Sucheston L, Sun YV, Taylor H, Taylor KC, Vitolins MZ, Wassertheil-Smoller S, Wojczynski MK, Xue L, Yanek LR, Zhao W, Zhou J, Zonderman ABDigital Object Identifier: Date added to catalog: 2014-04-04
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Journal Article MedStar Authors Catalog Article Available 23966867

Available online through MWHC library: 2005 - present

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 x 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 = 2.24x10(-8) for WC-adjusted-for-BMI, and rs6931262 at RREB1, p = 2.48x10(-8) for WHR-adjusted-for-BMI. However, neither signal was genome-wide significant after double GC-correction (LHX2: p = 6.5 x 10(-8); RREB1: p = 5.7 x 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.

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