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Genome-wide association of body fat distribution in African ancestry populations suggests new loci.
Tuesday,2014-04-01 10:58 America/Los_Angeles — poolea2
| Title | Genome-wide association of body fat distribution in African ancestry populations suggests new loci. |
| Publication Type | Journal Article |
| Year of Publication | 2013 |
| Authors | Liu, C-T, 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, W-M, 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, W Garvey, T, Pettaway, C, Nyante, S, Bandera, EV, Britton, AF, Zonderman, AB, Rasmussen-Torvik, LJ, Chen, Y-DI, Ding, J, Lohman, K, Kritchevsky, SB, Zhao, W, Peyser, PA, Kardia, SLR, Kabagambe, E, Broeckel, U, Chen, G, Zhou, J, Wassertheil-Smoller, S, Neuhouser, ML, Rampersaud, E, Psaty, B, Kooperberg, C, Manson, JAE, 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, SFA, 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, AL, North, KE, Fox, CS |
| Journal | PLoS Genet |
| Volume | 9 |
| Issue | 8 |
| Pagination | e1003681 |
| Date Published | 2013 |
| ISSN | 1553-7404 |
| Keywords | Adiposity, African Continental Ancestry Group, Body Fat Distribution, European Continental Ancestry Group, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Obesity, Polymorphism, Single Nucleotide, Waist-Hip Ratio |
| Abstract | <p>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.</p> |
| DOI | 10.1371/journal.pgen.1003681 |
| Alternate Journal | PLoS Genet. |
| PubMed ID | 23966867 |
| PubMed Central ID | PMC3744443 |
| Grant List | CA54281 / CA / NCI NIH HHS / United States N01-HB-72992 / HB / NHLBI NIH HHS / United States N02-HL-6-4278 / HL / NHLBI NIH HHS / United States N01-HC-25195 / HC / NHLBI NIH HHS / United States N01-HB-97068 / HB / NHLBI NIH HHS / United States R01-HL-088215 / HL / NHLBI NIH HHS / United States N01-HB-97053 / HB / NHLBI NIH HHS / United States N01-HB-72997 / HB / NHLBI NIH HHS / United States N01-HB-73003 / HB / NHLBI NIH HHS / United States 32105-6 / / PHS HHS / United States N01-HC-45205 / HC / NHLBI NIH HHS / United States UL1RR033176 / RR / NCRR NIH HHS / United States UL1TR000124 / TR / NCATS NIH HHS / United States P30 ES010126 / ES / NIEHS NIH HHS / United States ES007784 / ES / NIEHS NIH HHS / United States N01WH22110 / WH / WHI NIH HHS / United States N01-HC-05187 / HC / NHLBI NIH HHS / United States N01-HC-4804 / HC / NHLBI NIH HHS / United States R01-HL-071252 / HL / NHLBI NIH HHS / United States HL59684 / HL / NHLBI NIH HHS / United States S06GM008016-380111 / GM / NIGMS NIH HHS / United States U01 NS041588 / NS / NINDS NIH HHS / United States R01-HL-071258 / HL / NHLBI NIH HHS / United States UL1 TR000150 / TR / NCATS NIH HHS / United States U01 HL053934 / HL / NHLBI NIH HHS / United States MD002249 / MD / NIMHD NIH HHS / United States UL1-RR-025005 / RR / NCRR NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States HL071025-01A1 / HL / NHLBI NIH HHS / United States CA1326792 / CA / NCI NIH HHS / United States S06GM008016-320107 / GM / NIGMS NIH HHS / United States N01-HB-7299 / HB / NHLBI NIH HHS / United States R01 DK084350 / DK / NIDDK NIH HHS / United States R01-DK-8925601 / DK / NIDDK NIH HHS / United States R01 CA098663 / CA / NCI NIH HHS / United States N01-HB-97064 / HB / NHLBI NIH HHS / United States R01HL092577-01A1 / HL / NHLBI NIH HHS / United States Z01HG200362 / HG / NHGRI NIH HHS / United States M01RR00080 / RR / NCRR NIH HHS / United States HL085251 / HL / NHLBI NIH HHS / United States N01-HC-55022 / HC / 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