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

Publication ,  Journal Article
Ward-Caviness, C; Haynes, C; Blach, C; Dowdy, E; Gregory, SG; Shah, SH; Horne, BD; Kraus, WE; Hauser, ER
Published in: Hum Genet
December 2013

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.

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Published In

Hum Genet

DOI

EISSN

1432-1203

Publication Date

December 2013

Volume

132

Issue

12

Start / End Page

1371 / 1382

Location

Germany

Related Subject Headings

  • rho GTP-Binding Proteins
  • Smoking
  • Signal Transduction
  • Middle Aged
  • Male
  • Humans
  • Genetics & Heredity
  • Genetic Predisposition to Disease
  • Genetic Linkage
  • Gene-Environment Interaction
 

Citation

APA
Chicago
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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. Hum Genet, 132(12), 1371–1382. https://doi.org/10.1007/s00439-013-1339-7
Ward-Caviness, Cavin, Carol Haynes, Colette Blach, Elaine Dowdy, Simon G. Gregory, Svati H. Shah, Benjamin D. Horne, William E. Kraus, and Elizabeth R. Hauser. “Gene-smoking interactions in multiple Rho-GTPase pathway genes in an early-onset coronary artery disease cohort.Hum Genet 132, no. 12 (December 2013): 1371–82. https://doi.org/10.1007/s00439-013-1339-7.
Ward-Caviness C, Haynes C, Blach C, Dowdy E, Gregory SG, Shah SH, et al. Gene-smoking interactions in multiple Rho-GTPase pathway genes in an early-onset coronary artery disease cohort. Hum Genet. 2013 Dec;132(12):1371–82.
Ward-Caviness, Cavin, et al. “Gene-smoking interactions in multiple Rho-GTPase pathway genes in an early-onset coronary artery disease cohort.Hum Genet, vol. 132, no. 12, Dec. 2013, pp. 1371–82. Pubmed, doi:10.1007/s00439-013-1339-7.
Ward-Caviness C, Haynes C, Blach C, Dowdy E, Gregory SG, Shah SH, Horne BD, Kraus WE, Hauser ER. Gene-smoking interactions in multiple Rho-GTPase pathway genes in an early-onset coronary artery disease cohort. Hum Genet. 2013 Dec;132(12):1371–1382.
Journal cover image

Published In

Hum Genet

DOI

EISSN

1432-1203

Publication Date

December 2013

Volume

132

Issue

12

Start / End Page

1371 / 1382

Location

Germany

Related Subject Headings

  • rho GTP-Binding Proteins
  • Smoking
  • Signal Transduction
  • Middle Aged
  • Male
  • Humans
  • Genetics & Heredity
  • Genetic Predisposition to Disease
  • Genetic Linkage
  • Gene-Environment Interaction