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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

FST profile for nine genes with a significantly higher weighted-average FST. The X-axis indicates the chromosomal position (kb). See Table 3 for gene names. The average recombination rate (cM/MB) for the genes is: GRB2, 1.78; IKBKB, 0.76; ARHGEF1, 0.81; RIPK1, 2.06; PMVK, 1.07; BCL2L1, 0.86; IL4, 0.94; IL6, 1.10; F2, 0.66.
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Figure 6: FST profile for nine genes with a significantly higher weighted-average FST. The X-axis indicates the chromosomal position (kb). See Table 3 for gene names. The average recombination rate (cM/MB) for the genes is: GRB2, 1.78; IKBKB, 0.76; ARHGEF1, 0.81; RIPK1, 2.06; PMVK, 1.07; BCL2L1, 0.86; IL4, 0.94; IL6, 1.10; F2, 0.66.

Mentions: We also calculated a weighted-average FST, combining information over loci [35] that summarizes the levels of interpopulation differentiation in each gene. Genes with a significantly higher weighted-average FST are shown in Table 3. In total, there were signatures of local adaptation in nine genes (2.5%) – four genes in YRI vs. CEU and three genes in YRI vs. CHB + JPT, and three genes in CEU vs. CHB + JPT. Most of the genes are involved in 'immune response' (GRB2, IKBKB, IL4, IL6) and 'apoptosis' (ARHGEF1, RIPK1, BCL2L1, IL4, IL6), as well as one gene each in 'blood clotting' (F2) and 'lipoprotein metabolism' (PMVK). The distribution of FST along the sequence for these genes is shown in Figure 6, indicating multiple SNP loci with a significantly high FST.


Patterns of population differentiation of candidate genes for cardiovascular disease.

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

FST profile for nine genes with a significantly higher weighted-average FST. The X-axis indicates the chromosomal position (kb). See Table 3 for gene names. The average recombination rate (cM/MB) for the genes is: GRB2, 1.78; IKBKB, 0.76; ARHGEF1, 0.81; RIPK1, 2.06; PMVK, 1.07; BCL2L1, 0.86; IL4, 0.94; IL6, 1.10; F2, 0.66.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: FST profile for nine genes with a significantly higher weighted-average FST. The X-axis indicates the chromosomal position (kb). See Table 3 for gene names. The average recombination rate (cM/MB) for the genes is: GRB2, 1.78; IKBKB, 0.76; ARHGEF1, 0.81; RIPK1, 2.06; PMVK, 1.07; BCL2L1, 0.86; IL4, 0.94; IL6, 1.10; F2, 0.66.
Mentions: We also calculated a weighted-average FST, combining information over loci [35] that summarizes the levels of interpopulation differentiation in each gene. Genes with a significantly higher weighted-average FST are shown in Table 3. In total, there were signatures of local adaptation in nine genes (2.5%) – four genes in YRI vs. CEU and three genes in YRI vs. CHB + JPT, and three genes in CEU vs. CHB + JPT. Most of the genes are involved in 'immune response' (GRB2, IKBKB, IL4, IL6) and 'apoptosis' (ARHGEF1, RIPK1, BCL2L1, IL4, IL6), as well as one gene each in 'blood clotting' (F2) and 'lipoprotein metabolism' (PMVK). The distribution of FST along the sequence for these genes is shown in Figure 6, indicating multiple SNP loci with a significantly high FST.

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