Patterns of population differentiation of candidate genes for cardiovascular disease

BACKGROUND: The basis for ethnic differences in cardiovascular disease (CVD) susceptibility is not fully understood. We investigated patterns of population differentiation (F(ST)) of a set of genes in etiologic pathways of CVD among 3 ethnic groups: Yoruba in Nigeria (YRI), Utah residents with European ancestry (CEU), and Han Chinese (CHB) + Japanese (JPT). We identified 37 pathways implicated in CVD based on the PANTHER classification and 416 genes in these pathways were further studied; these genes belonged to 6 biological processes (apoptosis, blood circulation and gas exchange, blood clotting, homeostasis, immune response, and lipoprotein metabolism). Genotype data were obtained from the HapMap database. RESULTS: We calculated F(ST )for 15,559 common SNPs (minor allele frequency ≥ 0.10 in at least one population) in genes that co-segregated among the populations, as well as an average-weighted F(ST )for each gene. SNPs were classified as putatively functional (non-synonymous and untranslated regions) or non-functional (intronic and synonymous sites). Mean F(ST )values for common putatively functional variants were significantly higher than F(ST )values for nonfunctional variants. A significant variation in F(ST )was also seen based on biological processes; the processes of 'apoptosis' and 'lipoprotein metabolism' showed an excess of genes with high F(ST). Thus, putative functional SNPs in genes in etiologic pathways for CVD show greater population differentiation than non-functional SNPs and a significant variance of F(ST )values was noted among pairwise population comparisons for different biological processes. CONCLUSION: These results suggest a possible basis for varying susceptibility to CVD among ethnic groups.