Abstract 4110: Allele Frequencies of Functional SNPs in Candidate Genes for Cardiovascular Disease Differ by Ethnicity
Background: Susceptibility to cardiovascular disease (CVD) varies by ethnicity, possibly as a consequence of genetic or environmental factors or their interactions. We hypothesized that allele frequency of functional SNPs in CVD candidate genes would differ significantly across ethnic groups, compared to nonfunctional SNPs. We therefore assessed FST of SNPs in CVD candidate genes among 3 different ethnic groups. FST is a measure of population differentiation that quantifies the variance of allele frequency between populations to within population.
Methods: We calculated FST of 21,810 SNPs in ~ 416 CVD candidate genes belonging to 39 functional pathways (based on PANTHER, www.pantherdb.org) in 6 biological processes (coagulation, circulation and gas exchange, homeostasis, immune response, lipoprotein metabolism, and apoptosis). SNPs were classified as functional (nonsynonymous and untranslated regions) or nonfunctional (intronic and synonymous). Genotype data were obtained for Yoruba, European Americans, and Han Chinese from the HapMap database (www.hapma-p.org). Multiple pairwise comparisons were implemented in the ‘multcomp’ package using R.
Results: Mean FST values for common (minor allele frequency ≥ 0.30) functional variants were significantly higher than for nonfunctional SNPs. When analyzing functional pathways, FST of genes in ‘blood coagulation’, ‘Ras pathway’ and ‘Toll receptor signaling pathway’ differed significantly from other pathways, in pair wise comparisons among the 3 ethnic groups. When analyzing biological processes, FST of genes in coagulation, homeostasis, lipoprotein metabolism, and apoptosis differed significantly from other pathways in pair wise comparisons among the 3 ethnic groups.
Conclusion: Allele frequencies of common functional SNPs in CVD candidate genes vary significantly by ethnicity, in contrast to nonfunctional SNPs. The study of patterns of population differentiation of candidate genes for CVD may provide insight into the ethnic/geographic differences in cardiovascular risk.