Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Apr 20:12:55.
doi: 10.1186/1471-2350-12-55.

Geographic differences in allele frequencies of susceptibility SNPs for cardiovascular disease

Keyue Ding  1 , Iftikhar J Kullo
Affiliations

Geographic differences in allele frequencies of susceptibility SNPs for cardiovascular disease

Keyue Ding et al. BMC Med Genet. .

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 × 10⁻⁸. 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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Distribution of risk allele frequency (RAF) in HGDP populations. A. Differences in RAFs between any 2 of the 52 populations in the HGDP panel for the 158 SNPs associated with cardiovascular-diseases traits. B. Differences of RAF (formula image) for the comparison of a given tested region (eg, Africa) versus the rest of the world. Negative ΔF indicates that the risk allele has a higher frequency within the tested population than in the rest of the world (see methods section for the denotation of formula image and formula image).
Figure 2
Figure 2
Distribution of FST. A. Distribution of FST of 158 SNPs associated with cardiovascular diseases and related intermediate traits. The vertical bar shows the mean of global FST of these 158 SNPs (FST = 0.1042). B. Distribution of empirical global mean FST of 158 autosomal SNPs randomly sampled from HGDP database 1000 times. The distribution of minor allele frequency of the randomly selected 158 SNPs was matched to the observed 158 SNPs. The vertical bar shows the mean of global FST of 158 SNPs associated with cardiovascular diseases and related intermediate traits (FST = 0.1042). C. Distribution of empirical global FST of 2,036 markers assumed to be neutral, genotyped in 938 unrelated individuals form HGDP. Two vertical lines indicate 95% and 99% percentile of the global FST distribution. The vertical bars show the values of global FST value of 158 susceptibility SNPs in the present study.
Figure 3
Figure 3
Geographical distribution of risk (black) and wild-type (white) alleles in eight SNPs with a significantly higher FST among the 52 populations. In each subplot, the radius of a pie chart represents the sample size in a given population. The inserted barplot shows the average frequency of the risk allele among the seven geographic regions. From left to right, the bars indicate Africa, Middle East, Europe, Central South Asia, East Asia, America, and Oceania, respectively.
See this image and copyright information in PMC

References

    1. Keys A. Coronary heart disease in seven countries. Circulation. 1970;41(4 Suppl):1–211. - PubMed
    1. Anand SS, Yusuf S, Vuksan V, Devanesen S, Teo KK, Montague PA, Kelemen L, Yi C, Lonn E, Gerstein H. et al.Differences in risk factors, atherosclerosis, and cardiovascular disease between ethnic groups in Canada: the Study of Health Assessment and Risk in Ethnic groups (SHARE) Lancet. 2000;356(9226):279–284. doi: 10.1016/S0140-6736(00)02502-2. - DOI - PubMed
    1. Ding K, Kullo IJ. Genome-wide association studies for atherosclerotic vascular disease and its risk factors. Circ Cardiovasc Genet. 2009;2(1):63–72. doi: 10.1161/CIRCGENETICS.108.816751. - DOI - PMC - PubMed
    1. Ding K, Kullo IJ. Evolutionary genetics of coronary heart disease. Circulation. 2009;119(3):459–467. doi: 10.1161/CIRCULATIONAHA.108.809970. - DOI - PubMed
    1. Excoffier L, Ray N. Surfing during population expansions promotes genetic revolutions and structuration. Trends Ecol Evol. 2008;23(7):347–351. doi: 10.1016/j.tree.2008.04.004. - DOI - PubMed