Gene-smoking interactions in multiple Rho-GTPase pathway genes in an early-onset coronary artery disease cohort

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Ward-Caviness, C; Haynes, C; Blach, C; Dowdy, E; Gregory, SG; Shah, SH; Horne, BD; Kraus, WE; Hauser, ER

Published Date

  • December 1, 2013

Published In

Volume / Issue

  • 132 / 12

Start / End Page

  • 1371 - 1382

Electronic International Standard Serial Number (EISSN)

  • 1432-1203

International Standard Serial Number (ISSN)

  • 0340-6717

Digital Object Identifier (DOI)

  • 10.1007/s00439-013-1339-7

Citation Source

  • Scopus