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Genome-wide association study of smoking behaviours in patients with COPD.

Publication ,  Journal Article
Siedlinski, M; Cho, MH; Bakke, P; Gulsvik, A; Lomas, DA; Anderson, W; Kong, X; Rennard, SI; Beaty, TH; Hokanson, JE; Crapo, JD; Silverman, EK ...
Published in: Thorax
October 2011

Background Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and COPD severity. Previous genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) associated with the number of cigarettes smoked per day (CPD) and a dopamine beta-hydroxylase (DBH) locus associated with smoking cessation in multiple populations. Objective To identify SNPs associated with lifetime average and current CPD, age at smoking initiation, and smoking cessation in patients with COPD. Methods GWAS were conducted in four independent cohorts encompassing 3441 ever-smoking patients with COPD (Global Initiative for Obstructive Lung Disease stage II or higher). Untyped SNPs were imputed using the HapMap (phase II) panel. Results from all cohorts were meta-analysed. Results Several SNPs near the HLA region on chromosome 6p21 and in an intergenic region on chromosome 2q21 showed associations with age at smoking initiation, both with the lowest p=2×10(-7). No SNPs were associated with lifetime average CPD, current CPD or smoking cessation with p<10(-6). Nominally significant associations with candidate SNPs within cholinergic receptors, nicotinic, alpha 3/5 (CHRNA3/CHRNA5; eg, p=0.00011 for SNP rs1051730) and cytochrome P450, family 2, subfamily A, polypeptide 6 (CYP2A6; eg, p=2.78×10(-5) for a non-synonymous SNP rs1801272) regions were observed for lifetime average CPD, however only CYP2A6 showed evidence of significant association with current CPD. A candidate SNP (rs3025343) in DBH was significantly (p=0.015) associated with smoking cessation. Conclusion The authors identified two candidate regions associated with age at smoking initiation in patients with COPD. Associations of CHRNA3/CHRNA5 and CYP2A6 loci with CPD and DBH with smoking cessation are also likely of importance in the smoking behaviours of patients with COPD.

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Published In

Thorax

DOI

EISSN

1468-3296

Publication Date

October 2011

Volume

66

Issue

10

Start / End Page

894 / 902

Location

England

Related Subject Headings

  • United States
  • Smoking Cessation
  • Smoking
  • Respiratory System
  • Pulmonary Disease, Chronic Obstructive
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Incidence
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
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Siedlinski, M., Cho, M. H., Bakke, P., Gulsvik, A., Lomas, D. A., Anderson, W., … ECLIPSE Investigators, . (2011). Genome-wide association study of smoking behaviours in patients with COPD. Thorax, 66(10), 894–902. https://doi.org/10.1136/thoraxjnl-2011-200154
Siedlinski, Mateusz, Michael H. Cho, Per Bakke, Amund Gulsvik, David A. Lomas, Wayne Anderson, Xiangyang Kong, et al. “Genome-wide association study of smoking behaviours in patients with COPD.Thorax 66, no. 10 (October 2011): 894–902. https://doi.org/10.1136/thoraxjnl-2011-200154.
Siedlinski M, Cho MH, Bakke P, Gulsvik A, Lomas DA, Anderson W, et al. Genome-wide association study of smoking behaviours in patients with COPD. Thorax. 2011 Oct;66(10):894–902.
Siedlinski, Mateusz, et al. “Genome-wide association study of smoking behaviours in patients with COPD.Thorax, vol. 66, no. 10, Oct. 2011, pp. 894–902. Pubmed, doi:10.1136/thoraxjnl-2011-200154.
Siedlinski M, Cho MH, Bakke P, Gulsvik A, Lomas DA, Anderson W, Kong X, Rennard SI, Beaty TH, Hokanson JE, Crapo JD, Silverman EK, COPDGene Investigators, ECLIPSE Investigators. Genome-wide association study of smoking behaviours in patients with COPD. Thorax. 2011 Oct;66(10):894–902.

Published In

Thorax

DOI

EISSN

1468-3296

Publication Date

October 2011

Volume

66

Issue

10

Start / End Page

894 / 902

Location

England

Related Subject Headings

  • United States
  • Smoking Cessation
  • Smoking
  • Respiratory System
  • Pulmonary Disease, Chronic Obstructive
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Incidence
  • Humans