Faculty Collaboration Database

Genome-wide association of body fat distribution in African ancestry populations suggests new loci. PLoS Genet 2013;9(8):e1003681

Date

08/24/2013

Pubmed ID

23966867

Pubmed Central ID

PMC3744443

DOI

10.1371/journal.pgen.1003681

Scopus ID

2-s2.0-84884607859 (requires institutional sign-in at Scopus site)   104 Citations

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.

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

Author

Ulrich Broeckel MD Chief, Center Associate Director, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adiposity
Body Fat Distribution
Female
Genetic Loci
Genome-Wide Association Study
Humans
Male
Obesity
Polymorphism, Single Nucleotide
Waist-Hip Ratio