We performed a gene-smoking interaction analysis using families from an early-onset coronary artery disease cohort (GENECARD). This analysis was focused on validating and expanding results from previous studies implicating single nucleotide polymorphisms (SNPs) on chromosome 3 in smoking-mediated coronary artery disease. We analyzed 430 SNPs on chromosome 3 and identified 16 SNPs that showed a gene-smoking interaction at P < 0.05 using association in the presence of linkage-ordered subset analysis, a method that uses permutations of the data to empirically estimate the strength of the association signal. Seven of the 16 SNPs were in the Rho-GTPase pathway indicating a 1.87-fold enrichment for this pathway. A meta-analysis of gene-smoking interactions in three independent studies revealed that rs9289231 in KALRN had a Fisher's combined P value of 0.0017 for the interaction with smoking. In a gene-based meta-analysis KALRN had a P value of 0.026. Finally, a pathway-based analysis of the association results using WebGestalt revealed several enriched pathways including the regulation of the actin cytoskeleton pathway as defined by the Kyoto Encyclopedia of Genes and Genomes. © 2013 Springer-Verlag Berlin Heidelberg.
CITATION STYLE
Ward-Caviness, C., Haynes, C., Blach, C., Dowdy, E., Gregory, S. G., Shah, S. H., … Hauser, E. R. (2013). Gene-smoking interactions in multiple Rho-GTPase pathway genes in an early-onset coronary artery disease cohort. Human Genetics, 132(12), 1371–1382. https://doi.org/10.1007/s00439-013-1339-7
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