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.
Highlights
Obesity is an important public health problem, reaching epidemic proportions
We performed a collaborative meta-analysis in order to identify genetic loci associated with body fat distribution in African ancestry (AA) individuals using waist circumference (WC) and waist to hip ratio (WHR) as measures of fat distribution, with and without adjustment for body mass index (BMI)
We uncovered 2 genetic loci potentially associated with fat distribution: LHX2 in association with WC-adjusted-for-BMI and at RREB1 for WHR-adjusted-for-BMI
Summary
Obesity is an important public health problem, reaching epidemic proportions. The prevalence varies by ethnicity, with nearly one-third of European ancestry (EA) and almost one-half of African ancestry (AA) Americans considered obese [1]. Recent studies have suggested that body fat distribution, above and beyond generalized adiposity, is an important metric of metabolic health, as different fat compartments are associated with differential metabolic risk [2]. Waist circumference (WC) and waist to hip ratio (WHR) are established measures of body fat distribution [9] that differ by ethnicity [10,11] and demonstrate a genetic component. A recent meta-analysis of WHR in EA individuals identified 14 loci for body fat distribution [17]. Recent studies among EAs for percent body fat, fatty liver, visceral fat, and pericardial fat reported unique loci for fat distribution and ectopic fat depots above and beyond those associated with generalized adiposity [18,19,20,21]. The purpose of the present analysis was to perform a collaborative large-scale meta-analysis of waist-based traits in AA individuals
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