Genome-wide and candidate gene association study of cigarette smoking behaviors

Neil Caporaso, Fangyi Gu, Nilanjan Chatterjee, Jin Sheng-Chih, Kai Yu, Meredith Yeager, Constance Chen, Kevin Jacobs, William Wheeler, Maria Teresa Landi, Regina G. Ziegler, David J. Hunter, Stephen Chanock, Susan Hankinson, Peter Kraft, Andrew W. Bergen

Research output: Contribution to journalArticle

Abstract

The contribution of common genetic variation to one or more established smoking behaviors was investigated in a joint analysis of two genome wide association studies (GWAS) performed as part of the Cancer Genetic Markers of Susceptibility (CGEMS) project in 2,329 men from the Prostate, Lung, Colon and Ovarian (PLCO) Trial, and 2,282 women from the Nurses' Health Study (NHS). We analyzed seven measures of smoking behavior, four continuous (cigarettes per day [CPD], age at initiation of smoking, duration of smoking, and pack years), and three binary (ever versus never smoking, ≤10 versus ≥10 cigarettes per day [CPDBI], and current versus former smoking). Association testing for each single nucleotide polymorphism (SNP) was conducted by study and adjusted for age, cohabitation/marital status, education, site, and principal components of population substructure. None of the SNPs achieved genome-wide significance (p<10-7) in any combined analysis pooling evidence for association across the two studies; we observed between two and seven SNPs with p<10-5 for each of the seven measures. In the chr15q25.1 region spanning the nicotinic receptors CHRNA3 and CHRNA5, we identified multiple SNPs associated with CPD (p<10-3), including rs1051730, which has been associated with nicotine dependence, smoking intensity and lung cancer risk. In parallel, we selected 11,199 SNPs drawn from 359 a priori candidate genes and performed individual-gene and gene-group analyses. After adjusting for multiple tests conducted within each gene, we identified between two and five genes associated with each measure of smoking behavior. Besides CHRNA3 and CHRNA5, MAOA was associated with CPDBI (gene-level p<5.4×10-5), our analysis provides independent replication of the association between the chr15q25.1 region and smoking intensity and data for multiple other loci associated with smoking behavior that merit further follow-up.

Original languageEnglish (US)
Article numbere4653
JournalPLoS One
Volume4
Issue number2
DOIs
StatePublished - 2009
Externally publishedYes

Fingerprint

smoking (habit)
Genetic Association Studies
Tobacco Products
Genes
Smoking
Genome
genome
cigarettes
Single Nucleotide Polymorphism
genes
marital status
nicotine
nurses
lung neoplasms
single nucleotide polymorphism
colon
genotype-phenotype correlation
education
Nicotinic Receptors
Polymorphism

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Caporaso, N., Gu, F., Chatterjee, N., Sheng-Chih, J., Yu, K., Yeager, M., ... Bergen, A. W. (2009). Genome-wide and candidate gene association study of cigarette smoking behaviors. PLoS One, 4(2), [e4653]. https://doi.org/10.1371/journal.pone.0004653

Genome-wide and candidate gene association study of cigarette smoking behaviors. / Caporaso, Neil; Gu, Fangyi; Chatterjee, Nilanjan; Sheng-Chih, Jin; Yu, Kai; Yeager, Meredith; Chen, Constance; Jacobs, Kevin; Wheeler, William; Landi, Maria Teresa; Ziegler, Regina G.; Hunter, David J.; Chanock, Stephen; Hankinson, Susan; Kraft, Peter; Bergen, Andrew W.

In: PLoS One, Vol. 4, No. 2, e4653, 2009.

Research output: Contribution to journalArticle

Caporaso, N, Gu, F, Chatterjee, N, Sheng-Chih, J, Yu, K, Yeager, M, Chen, C, Jacobs, K, Wheeler, W, Landi, MT, Ziegler, RG, Hunter, DJ, Chanock, S, Hankinson, S, Kraft, P & Bergen, AW 2009, 'Genome-wide and candidate gene association study of cigarette smoking behaviors', PLoS One, vol. 4, no. 2, e4653. https://doi.org/10.1371/journal.pone.0004653
Caporaso, Neil ; Gu, Fangyi ; Chatterjee, Nilanjan ; Sheng-Chih, Jin ; Yu, Kai ; Yeager, Meredith ; Chen, Constance ; Jacobs, Kevin ; Wheeler, William ; Landi, Maria Teresa ; Ziegler, Regina G. ; Hunter, David J. ; Chanock, Stephen ; Hankinson, Susan ; Kraft, Peter ; Bergen, Andrew W. / Genome-wide and candidate gene association study of cigarette smoking behaviors. In: PLoS One. 2009 ; Vol. 4, No. 2.
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