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Geographic differences in allele frequencies of susceptibility SNPs for cardiovascular disease.

ABSTRACT: BACKGROUND: We hypothesized that the frequencies of risk alleles of SNPs mediating susceptibility to cardiovascular diseases differ among populations of varying geographic origin and that population-specific selection has operated on some of these variants. METHODS: From the database of genome-wide association studies (GWAS), we selected 36 cardiovascular phenotypes including coronary heart disease, hypertension, and stroke, as well as related quantitative traits (eg, body mass index and plasma lipid levels). We identified 292 SNPs in 270 genes associated with a disease or trait at P < 5 × 10??. As part of the Human Genome-Diversity Project (HGDP), 158 (54.1%) of these SNPs have been genotyped in 938 individuals belonging to 52 populations from seven geographic areas. A measure of population differentiation, F(ST), was calculated to quantify differences in risk allele frequencies (RAFs) among populations and geographic areas. RESULTS: Large differences in RAFs were noted in populations of Africa, East Asia, America and Oceania, when compared with other geographic regions. The mean global F(ST) (0.1042) for 158 SNPs among the populations was not significantly higher than the mean global F(ST) of 158 autosomal SNPs randomly sampled from the HGDP database. Significantly higher global F(ST) (P < 0.05) was noted in eight SNPs, based on an empirical distribution of global F(ST) of 2036 putatively neutral SNPs. For four of these SNPs, additional evidence of selection was noted based on the integrated Haplotype Score. CONCLUSION: Large differences in RAFs for a set of common SNPs that influence risk of cardiovascular disease were noted between the major world populations. Pairwise comparisons revealed RAF differences for at least eight SNPs that might be due to population-specific selection or demographic factors. These findings are relevant to a better understanding of geographic variation in the prevalence of cardiovascular disease.

SUBMITTER: Ding K

PROVIDER: S-EPMC3103418 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Geographic differences in allele frequencies of susceptibility SNPs for cardiovascular disease.

Ding Keyue K Kullo Iftikhar J IJ

BMC medical genetics 20110420

<h4>Background</h4>We hypothesized that the frequencies of risk alleles of SNPs mediating susceptibility to cardiovascular diseases differ among populations of varying geographic origin and that population-specific selection has operated on some of these variants.<h4>Methods</h4>From the database of genome-wide association studies (GWAS), we selected 36 cardiovascular phenotypes including coronary heart disease, hypertension, and stroke, as well as related quantitative traits (eg, body mass inde ...[more]

PMID: 21507254

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Project description:BackgroundObesity is emerging as a global health problem, with more than one-third of the world's adult population being overweight or obese. In this study, we investigated worldwide population differentiation in allele frequencies of obesity-associated SNPs (single nucleotide polymorphisms).ResultsWe collected a total of 225 obesity-associated SNPs from a public database. Their population-level allele frequencies were derived based on the genotype data from 1000 Genomes Project (phase 3). We used hypergeometric model to assess whether the effect allele at a given SNP is significantly enriched or depleted in each of the 26 populations surveyed in the 1000 Genomes Project with respect to the overall pooled population. Our results indicate that 195 out of 225 SNPs (86.7%) possess effect alleles significantly enriched or depleted in at least one of the 26 populations. Populations within the same continental group exhibit similar allele enrichment/depletion patterns whereas inter-continental populations show distinct patterns. Among the 225 SNPs, 15 SNPs cluster in the first intron region of the FTO gene, which is a major gene associated with body-mass index (BMI) and fat mass. African populations exhibit much smaller blocks of LD (linkage disequilibrium) among these15 SNPs while European and Asian populations have larger blocks. To estimate the cumulative effect of all variants associated with obesity, we developed the personal composite genetic risk score for obesity. Our results indicate that the East Asian populations have the lowest averages of the composite risk scores, whereas three European populations have the highest averages. In addition, the population-level average of composite genetic risk scores is significantly correlated (R2 = 0.35, P = 0.0060) with obesity prevalence.ConclusionsWe have detected substantial population differentiation in allele frequencies of obesity-associated SNPs. The results will help elucidate the genetic basis which may contribute to population disparities in obesity prevalence.

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Geographic differences in allele frequencies of susceptibility SNPs for cardiovascular disease.

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Geographic differences in allele frequencies of susceptibility SNPs for cardiovascular disease.

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