Association of DXA-derived bone mineral density and fat mass with african ancestry

Context: Both genes and environment have been implicated in determining the complex body composition phenotypes in individuals of European ancestry; however, few studies have been conducted in other race/ethnic groups. Objective: We conducted a genome-wide admixture mapping study in an attempt to localize novel genomic regions associated with genetic ancestry. Setting/Participants: We selected a sample of 842 African-American women from the Women's Health Initiative single nucleotide polymorphism (SNP) Health Association Resource for whom several dual-energy X-ray absorptiometry (DXA)-derived bone mineral density (BMD) and fat mass phenotypes were available. Methods: We derived both global and local ancestry estimates for each individual from Affymetrix 6.0 data and analyzed the correlation of DXA phenotypes with global African ancestry. For each phenotype, we examined the association of local genetic ancestry (number of African ancestral alleles at each marker) and each DXA phenotype at 570 282 markers acrossthe genome in additive models with adjustment for important covariates. Results: We identified statistically significant correlations of whole-body fat mass, trunk fat mass, and all 6 measures of BMD with a proportion of African ancestry. Genome-wide (admixture) significance for femoral neck BMD was achieved across 2 regions -3.7 MB and 0.3 MB on chromosome 19q13; similarly, total hip and intertrochanter BMD were associated with local ancestry in these regions. Trunk fat was the most significant fat mass phenotype showing strong, but not genomewide significant associations on chromosome Xp22. Conclusions: Our results suggest that genomic regions in postmenopausal African-American women contribute to variance in BMD and fat mass existence and warrant further study.