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

Abstract

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.

Estimating the contribution of genetic variants to difference in incidence of disease between population groups

“…21 These results suggest that the genetic factors predisposing to obesity in African Americans at FTO may be different from that in other populations, although an alternative explanation for these observations is that the causal variant has not been identified, and the linkage disequilibrium patterns to the causal variant are different in African and non-African populations. 22 GC can be used not only for genetic variants but an equivalent expression can be used also for environmental factors. The same concept can be used to compare contributions from genetic variants, environmental factors and joint effects of gene and environment to the difference in incidence between populations for a given disease.…”

Population Genetics in the Genomic Era

“…Using admixture mapping, many complex diseases associated loci have been identified by selected AIMs [99,[182][183][184]. For example, admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men, which can be replicated by later GWAS [185].…”

Genetic Ancestry Is Associated With Systolic Blood Pressure and Glucose in Brazilian Children and Adolescents

“…Studies in the US population, one of the most wellstudied admixed populations, show a positive correlation between African ancestry and higher values of body mass index (BMI), weight, leg length, lean mass, bone mineral density and lower values of fat mass, and total, intra-and subcutaneous abdominal fat [9,13,14]. Conversely, European ancestry has been inversely correlated with lean body mass, BMI, weight, hip circumference, and skinfold thickness subscapularis, and positively correlated with waist circumference adjusted for BMI [14][15][16].…”