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, Harvey Coxson, Lisa Edwards, Katharine Knobil, William MacNee, Ruth Tal-Singer, Jørgen Vestbo, Julie Yates, Jeffrey CurtisElla Kazerooni, Nicola Hanania, Philip Alapat, Venkata Bandi, Kalpalatha Guntupalli, Elizabeth Guy, Antara Mallampalli, Charles Trinh, Mustafa Atik, Dawn DeMeo, Craig Hersh, George Washko, Francine Jacobson, Graham Barr, Byron Thomashow, John Austin, Neil MacIntyre, Lacey Washington, H. Page McAdams, Richard Rosiello, Timothy Bresnahan, Charlene McEvoy, Joseph Tashjian, Robert Wise, Nadia Hansel, Robert Brown, Gregory Diette, Richard Casaburi, Janos Porszasz, Hans Fischer, Matt Budoff, Amir Sharafkhaneh, Hirani Kamal, Roham Darvishi, Dennis Niewoehner, Tadashi Allen, Quentin Anderson, Kathryn Rice, Marilyn Foreman, Gloria Westney, Eugene Berkowitz, Russell Bowler, Adam Friedlander, David Lynch, Joyce Schroeder, John Newell, Gerard Criner, Victor Kim, Nathaniel Marchetti, Aditi Satti, A. James Mamary, Robert Steiner, Chandra Dass, William Bailey, Mark Dransfield, Hrudaya Nath, Joe Ramsdell, Paul Friedman, Geoffrey McLennan, Edwin J.R. Van Beek, Brad Thompson, Dwight Look, Fernando Martinez, Mei Lan Han, Christine Wendt, Frank Sciurba, Joel Weissfeld, Carl Fuhrman, Jessica Bon, Antonio Anzueto, Sandra Adams, Carlos Orozco, Mario Ruiz

Research output: Contribution to journalArticle

77 Scopus citations

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<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.

Original languageEnglish (US)
Pages (from-to)894-902
Number of pages9
JournalThorax
Volume66
Issue number10
DOIs
StatePublished - Oct 2011
Externally publishedYes

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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    Siedlinski, M., Cho, M. H., Bakke, P., Gulsvik, A., Lomas, D. A., Anderson, W., Kong, X., Rennard, S. I., Beaty, T. H., Hokanson, J. E., Crapo, J. D., Silverman, E. K., Coxson, H., Edwards, L., Knobil, K., MacNee, W., Tal-Singer, R., Vestbo, J., Yates, J., ... Ruiz, M. (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