title: Gene-smoking interactions in multiple Rho-GTPase pathway genes in an early-onset coronary artery disease cohort.
abstract: 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.
authors.affiliation: Center for Human Genetics, School of Medicine, Duke University Medical Center, Box 3382, Durham, NC, 27710, USA, cavin.wardcaviness@gmail.com.
authors.forename: Cavin
authors.initials: C
authors.lastname: Ward-Caviness
authors.forename: Carol
authors.initials: C
authors.lastname: Haynes
authors.forename: Colette
authors.initials: C
authors.lastname: Blach
authors.forename: Elaine
authors.initials: E
authors.lastname: Dowdy
authors.forename: Simon G
authors.initials: SG
authors.lastname: Gregory
authors.forename: Svati H
authors.initials: SH
authors.lastname: Shah
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Horne
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Hauser
mesh_terms: D000328:Adult; D017668:Age of Onset; D002893:Chromosomes, Human, Pair 3; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000235:genetics; D012907:Smoking / Q000453:epidemiology* / Q000235:genetics*; D020741:rho GTP-Binding Proteins / Q000235:genetics*
chemical_list: D020741:rho GTP-Binding Proteins
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