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

Mateusz Siedlinski, Michael H Cho, Per Bakke, Amund Gulsvik, David A Lomas, Wayne Anderson, Xiangyang Kong, Stephen I Rennard, Terri H Beaty, John E Hokanson, James D Crapo, Edwin K Silverman, COPDGene Investigators, Bill MacNee

Research output: Contribution to journalArticlepeer-review

Abstract

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
Original languageEnglish
Pages (from-to)894-902
Number of pages9
JournalThorax
Volume66
Issue number10
DOIs
Publication statusPublished - 2011

Keywords

  • clinical trial, phase II
  • Comparative Study
  • multicenter study
  • Randomized controlled trial

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