May 24, 2009

European admixture and Body Mass Index in African Americans

While a larger portion of African ancestry in African Americans is associated with higher probability of obesity, a larger portion of African ancestry in a particular locus actually reduced the probability of obesity. This underscores the importance of not relying on first-order approximations (racial identity) when more detailed information is available.

From the paper:
We have carried out admixture mapping analyses to search for genomic regions associated with BMI. This pooled analysis of samples from 14 studies is the largest admixture scan reported to date. In more than 15,000 individuals, we identified a locus on chromosome 5 where greater local European ancestry was associated with higher levels of BMI (P = 5.8×10−7), and two regions on chromosome X where greater local European ancestry was associated with lower levels of BMI (both P<5.0×10−6). Each of these three associations was above and beyond the contribution of genome-wide European ancestry, and each reached genome-wide significance.


The inverse correlation between BMI and percentage of European ancestry estimated on the genome-wide scale confirmed the results from previous studies of smaller sample size and fewer markers [29],[30]. However, while genome-wide ancestry is likely correlated with local ancestry, it cannot fully capture ancestry information at each locus as there exists variation across the genome in the effects of locus-specific ancestry on obesity. In particular, local European ancestry at 5q13.3 was positively associated with BMI, providing the first evidence of a genome-wide significant ancestry association being in the opposite direction to the overall epidemiological association.
PLoS Genetics doi:10.1371/journal.pgen.1000490

Admixture Mapping of 15,280 African Americans Identifies Obesity Susceptibility Loci on Chromosomes 5 and X

Ching-Yu Cheng et al.


The prevalence of obesity (body mass index (BMI) ≥30 kg/m2) is higher in African Americans than in European Americans, even after adjustment for socioeconomic factors, suggesting that genetic factors may explain some of the difference. To identify genetic loci influencing BMI, we carried out a pooled analysis of genome-wide admixture mapping scans in 15,280 African Americans from 14 epidemiologic studies. Samples were genotyped at a median of 1,411 ancestry-informative markers. After adjusting for age, sex, and study, BMI was analyzed both as a dichotomized (top 20% versus bottom 20%) and a continuous trait. We found that a higher percentage of European ancestry was significantly correlated with lower BMI (ρ = −0.042, P = 1.6×10−7). In the dichotomized analysis, we detected two loci on chromosome X as associated with increased African ancestry: the first at Xq25 (locus-specific LOD = 5.94; genome-wide score = 3.22; case-control Z = −3.94); and the second at Xq13.1 (locus-specific LOD = 2.22; case-control Z = −4.62). Quantitative analysis identified a third locus at 5q13.3 where higher BMI was highly significantly associated with greater European ancestry (locus-specific LOD = 6.27; genome-wide score = 3.46). Further mapping studies with dense sets of markers will be necessary to identify the alleles in these regions of chromosomes X and 5 that may be associated with variation in BMI.


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