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Patterns of population differentiation of candidate genes for cardiovascular disease.

Kullo IJ, Ding K - BMC Genet. (2007)

Bottom Line: Mean FST values for common putatively functional variants were significantly higher than FST values for nonfunctional variants.Thus, putative functional SNPs in genes in etiologic pathways for CVD show greater population differentiation than non-functional SNPs and a significant variance of FST values was noted among pairwise population comparisons for different biological processes.These results suggest a possible basis for varying susceptibility to CVD among ethnic groups.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA. kullo.iftikhar@mayo.edu

ABSTRACT

Background: The basis for ethnic differences in cardiovascular disease (CVD) susceptibility is not fully understood. We investigated patterns of population differentiation (FST) 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 FST for 15,559 common SNPs (minor allele frequency > or = 0.10 in at least one population) in genes that co-segregated among the populations, as well as an average-weighted FST for each gene. SNPs were classified as putatively functional (non-synonymous and untranslated regions) or non-functional (intronic and synonymous sites). Mean FST values for common putatively functional variants were significantly higher than FST values for nonfunctional variants. A significant variation in FST was also seen based on biological processes; the processes of 'apoptosis' and 'lipoprotein metabolism' showed an excess of genes with high FST. Thus, putative functional SNPs in genes in etiologic pathways for CVD show greater population differentiation than non-functional SNPs and a significant variance of FST 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.

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Related in: MedlinePlus

Mean FST values for SNPs of different categories, conditioned on MAF. YRI, Yoruba in Ibadan, Nigeria; CEU, Utah residents with ancestry from northern and western Europe, CHB, Han Chinese in Beijing, China, and JPT, Japanese in Tokyo, Japan
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Figure 2: Mean FST values for SNPs of different categories, conditioned on MAF. YRI, Yoruba in Ibadan, Nigeria; CEU, Utah residents with ancestry from northern and western Europe, CHB, Han Chinese in Beijing, China, and JPT, Japanese in Tokyo, Japan

Mentions: To assess differences in the distribution of combined FST values according to different categories of SNPs, we plotted the correlation between mean pairwise FST and MAF according to the five different SNPs categories (Figure 2). The mean FST values for SNPs of different categories conditioned on MAF are listed in Table S2 (see additional file 1). Using analysis of variance (ANOVA), we found that the pairwise mean FST values in CEU vs. CHB + JPT varied significantly among different SNP categories (P = 0.019) by analysis of variance, but not in YRI vs. CEU (P = 0.273) and YRI vs. CHB + JPT (P = 0.124) (see Methods). In addition, pairwise mean FST values between any two populations differed with MAF (P < 2.2 × 10-16), and there was a significant interaction of logarithm transformed MAF × category (P < 3.3 × 10-5), indicating that the effect of SNP category was modified by MAF.


Patterns of population differentiation of candidate genes for cardiovascular disease.

Kullo IJ, Ding K - BMC Genet. (2007)

Mean FST values for SNPs of different categories, conditioned on MAF. YRI, Yoruba in Ibadan, Nigeria; CEU, Utah residents with ancestry from northern and western Europe, CHB, Han Chinese in Beijing, China, and JPT, Japanese in Tokyo, Japan
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1937006&req=5

Figure 2: Mean FST values for SNPs of different categories, conditioned on MAF. YRI, Yoruba in Ibadan, Nigeria; CEU, Utah residents with ancestry from northern and western Europe, CHB, Han Chinese in Beijing, China, and JPT, Japanese in Tokyo, Japan
Mentions: To assess differences in the distribution of combined FST values according to different categories of SNPs, we plotted the correlation between mean pairwise FST and MAF according to the five different SNPs categories (Figure 2). The mean FST values for SNPs of different categories conditioned on MAF are listed in Table S2 (see additional file 1). Using analysis of variance (ANOVA), we found that the pairwise mean FST values in CEU vs. CHB + JPT varied significantly among different SNP categories (P = 0.019) by analysis of variance, but not in YRI vs. CEU (P = 0.273) and YRI vs. CHB + JPT (P = 0.124) (see Methods). In addition, pairwise mean FST values between any two populations differed with MAF (P < 2.2 × 10-16), and there was a significant interaction of logarithm transformed MAF × category (P < 3.3 × 10-5), indicating that the effect of SNP category was modified by MAF.

Bottom Line: Mean FST values for common putatively functional variants were significantly higher than FST values for nonfunctional variants.Thus, putative functional SNPs in genes in etiologic pathways for CVD show greater population differentiation than non-functional SNPs and a significant variance of FST values was noted among pairwise population comparisons for different biological processes.These results suggest a possible basis for varying susceptibility to CVD among ethnic groups.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA. kullo.iftikhar@mayo.edu

ABSTRACT

Background: The basis for ethnic differences in cardiovascular disease (CVD) susceptibility is not fully understood. We investigated patterns of population differentiation (FST) 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 FST for 15,559 common SNPs (minor allele frequency > or = 0.10 in at least one population) in genes that co-segregated among the populations, as well as an average-weighted FST for each gene. SNPs were classified as putatively functional (non-synonymous and untranslated regions) or non-functional (intronic and synonymous sites). Mean FST values for common putatively functional variants were significantly higher than FST values for nonfunctional variants. A significant variation in FST was also seen based on biological processes; the processes of 'apoptosis' and 'lipoprotein metabolism' showed an excess of genes with high FST. Thus, putative functional SNPs in genes in etiologic pathways for CVD show greater population differentiation than non-functional SNPs and a significant variance of FST 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.

Show MeSH
Related in: MedlinePlus