| Purpose. Obesity is influenced by both environmental and genetic factors. There is convincing evidence that the prevalence of obesity is higher in African Americans than whites. This leads to the hypothesis that differences in genetic background may contribute to the racial/ethnic disparity. We performed genome-wide admixture mapping scans of obesity-related traits in African Americans from the Atherosclerosis Risk in Communities (ARIC) Study and 13 other epidemiological studies in the U.S.;Methods. We included 3,522 African Americans from the ARIC Study and 11,758 from the other 13 studies. These samples were genotyped for an average of ∼1,532 ancestry-informative SNP markers. In the ARIC study, obesity-related traits, such as body mass index (BMI), weight and waist circumference were used for analysis, after correcting for socioeconomic factors. In the pooled analysis of 15,280 samples, BMI was used for testing its association with ancestry. We used a Bayesian method as implemented by the ANCESTRYMAP software to estimate overall European ancestry and to perform admixture mapping analysis with case-only (locus-specific LOD and genome-wide score), case-control (Z score), and quantitative approaches.;Results. We found that a higher European ancestry proportion was significantly correlated with lower BMI (P < 0.001). In the ARIC Study, we identified a locus at 2p23.3 to be suggestively associated with BMI (locus-specific LOD = 4.11) and weight (locus-specific LOD 4.07). The pooled analysis of 15,280 samples revealed the existence of loci with excess African ancestry among obese cases at Xq25 at a genome-wide significant level (locus-specific LOD = 5.94; genome-wide score = 3.22, and case-control score of Z = -3.94) and at Xq13.1 (locus-specific LOD = 2.22), where there is the most statistically significant case-control statistic (Z score = -4.62). In the quantitative analysis of BMI, we found an additional peak at 5q13.3 corresponding to a rise in European ancestry (locus-specific LOD = 6.27; genome-wide score = 3.46).;Conclusions. Our results suggest that genetic differences exist and account for differences in the risk of obesity between African and European Americans. Follow-up fine mapping across the admixture peak will be crucial to determine whether these regions harbor genetic variants predisposing to obesity. |
