MedStar Authors catalog › Details for: Genome-wide association of body fat distribution in African ancestry populations suggests new loci.
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Genome-wide association of body fat distribution in African ancestry populations suggests new loci.

by Howard, Barbara V.
Citation: PLoS Genetics. 9(8):e1003681, 2013..Journal: PLoS genetics.ISSN: 1553-7390.Full author list: Liu CT; Monda KL; Taylor KC; Lange L; Demerath EW; Palmas W; Wojczynski MK; Ellis JC; Vitolins MZ; Liu S; Papanicolaou GJ; Irvin MR; Xue L; Griffin PJ; Nalls MA; Adeyemo A; Liu J; Li G; Ruiz-Narvaez EA; Chen WM; Chen F; Henderson BE; Millikan RC; Ambrosone CB; Strom SS; Guo X; Andrews JS; Sun YV; Mosley TH; Yanek LR; Shriner D; Haritunians T; Rotter JI; Speliotes EK; Smith M; Rosenberg L; Mychaleckyj J; Nayak U; Spruill I; Garvey WT; Pettaway C; Nyante S; Bandera EV; Britton AF; Zonderman AB; Rasmussen-Torvik LJ; Chen YD; Ding J; Lohman K; Kritchevsky SB; Zhao W; Peyser PA; Kardia SL; Kabagambe E; Broeckel U; Chen G; Zhou J; Wassertheil-Smoller S; Neuhouser ML; Rampersaud E; Psaty B; Kooperberg C; Manson JE; Kuller LH; Ochs-Balcom HM; Johnson KC; Sucheston L; Ordovas JM; Palmer JR; Haiman CA; McKnight B; Howard BV; Becker DM; Bielak LF; Liu Y; Allison MA; Grant SF; Burke GL; Patel SR; Schreiner PJ; Borecki IB; Evans MK; Taylor H; Sale MM; Howard V; Carlson CS; Rotimi CN; Cushman M; Harris TB; Reiner AP; Cupples LA; North KE; Fox CS.UI/PMID: 23966867.Subject(s): Adiposity/ge [Genetics] | *African Continental Ancestry Group/ge [Genetics] | *Body Fat Distribution | European Continental Ancestry Group/ge [Genetics] | Female | Genetic Loci | *Genome-Wide Association Study | Humans | Male | *Obesity/ge [Genetics] | Obesity/pa [Pathology] | Polymorphism, Single Nucleotide | Waist-Hip RatioInstitution(s): MedStar Health Research InstituteActivity type: Journal Article.Medline 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.SOnline resources: Click here to access online Digital Object Identifier: (Click here) Abbreviated citation: PLoS Genet. 9(8):e1003681, 2013.Local Holdings: Available online through MWHC library: 2005 - present.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 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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