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 Israel 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 Curtis & 73 others Ella 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

75 Citations (Scopus)

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 - Jan 1 2011

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Genome-Wide Association Study
Chronic Obstructive Pulmonary Disease
Single Nucleotide Polymorphism
Smoking
Tobacco Products
Smoking Cessation
Dopamine beta-Hydroxylase
Chromosomes
HapMap Project
Obstructive Lung Diseases
Intergenic DNA
Cholinergic Receptors

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Siedlinski, M., Cho, M. H., Bakke, P., Gulsvik, A., Lomas, D. A., Anderson, W., ... 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

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

In: Thorax, Vol. 66, No. 10, 01.01.2011, p. 894-902.

Research output: Contribution to journalArticle

Siedlinski, M, Cho, MH, Bakke, P, Gulsvik, A, Lomas, DA, Anderson, W, Kong, X, Rennard, SI, Beaty, TH, Hokanson, JE, Crapo, JD, Silverman, EK, Coxson, H, Edwards, L, Knobil, K, MacNee, W, Tal-Singer, R, Vestbo, J, Yates, J, Curtis, J, Kazerooni, E, Hanania, N, Alapat, P, Bandi, V, Guntupalli, K, Guy, E, Mallampalli, A, Trinh, C, Atik, M, DeMeo, D, Hersh, C, Washko, G, Jacobson, F, Barr, G, Thomashow, B, Austin, J, MacIntyre, N, Washington, L, McAdams, HP, Rosiello, R, Bresnahan, T, McEvoy, C, Tashjian, J, Wise, R, Hansel, N, Brown, R, Diette, G, Casaburi, R, Porszasz, J, Fischer, H, Budoff, M, Sharafkhaneh, A, Kamal, H, Darvishi, R, Niewoehner, D, Allen, T, Anderson, Q, Rice, K, Foreman, M, Westney, G, Berkowitz, E, Bowler, R, Friedlander, A, Lynch, D, Schroeder, J, Newell, J, Criner, G, Kim, V, Marchetti, N, Satti, A, Mamary, AJ, Steiner, R, Dass, C, Bailey, W, Dransfield, M, Nath, H, Ramsdell, J, Friedman, P, McLennan, G, Van Beek, EJR, Thompson, B, Look, D, Martinez, F, Han, ML, Wendt, C, Sciurba, F, Weissfeld, J, Fuhrman, C, Bon, J, Anzueto, A, Adams, S, Orozco, C & Ruiz, M 2011, 'Genome-wide association study of smoking behaviours in patients with COPD', Thorax, vol. 66, no. 10, pp. 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 Jan 1;66(10):894-902. https://doi.org/10.1136/thoraxjnl-2011-200154
Siedlinski, Mateusz ; Cho, Michael H. ; Bakke, Per ; Gulsvik, Amund ; Lomas, David A. ; Anderson, Wayne ; Kong, Xiangyang ; Rennard, Stephen Israel ; Beaty, Terri H. ; Hokanson, John E. ; Crapo, James D. ; Silverman, Edwin K. ; Coxson, Harvey ; Edwards, Lisa ; Knobil, Katharine ; MacNee, William ; Tal-Singer, Ruth ; Vestbo, Jørgen ; Yates, Julie ; Curtis, Jeffrey ; Kazerooni, Ella ; Hanania, Nicola ; Alapat, Philip ; Bandi, Venkata ; Guntupalli, Kalpalatha ; Guy, Elizabeth ; Mallampalli, Antara ; Trinh, Charles ; Atik, Mustafa ; DeMeo, Dawn ; Hersh, Craig ; Washko, George ; Jacobson, Francine ; Barr, Graham ; Thomashow, Byron ; Austin, John ; MacIntyre, Neil ; Washington, Lacey ; McAdams, H. Page ; Rosiello, Richard ; Bresnahan, Timothy ; McEvoy, Charlene ; Tashjian, Joseph ; Wise, Robert ; Hansel, Nadia ; Brown, Robert ; Diette, Gregory ; Casaburi, Richard ; Porszasz, Janos ; Fischer, Hans ; Budoff, Matt ; Sharafkhaneh, Amir ; Kamal, Hirani ; Darvishi, Roham ; Niewoehner, Dennis ; Allen, Tadashi ; Anderson, Quentin ; Rice, Kathryn ; Foreman, Marilyn ; Westney, Gloria ; Berkowitz, Eugene ; Bowler, Russell ; Friedlander, Adam ; Lynch, David ; Schroeder, Joyce ; Newell, John ; Criner, Gerard ; Kim, Victor ; Marchetti, Nathaniel ; Satti, Aditi ; Mamary, A. James ; Steiner, Robert ; Dass, Chandra ; Bailey, William ; Dransfield, Mark ; Nath, Hrudaya ; Ramsdell, Joe ; Friedman, Paul ; McLennan, Geoffrey ; Van Beek, Edwin J.R. ; Thompson, Brad ; Look, Dwight ; Martinez, Fernando ; Han, Mei Lan ; Wendt, Christine ; Sciurba, Frank ; Weissfeld, Joel ; Fuhrman, Carl ; Bon, Jessica ; Anzueto, Antonio ; Adams, Sandra ; Orozco, Carlos ; Ruiz, Mario. / Genome-wide association study of smoking behaviours in patients with COPD. In: Thorax. 2011 ; Vol. 66, No. 10. pp. 894-902.
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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.",
author = "Mateusz Siedlinski and Cho, {Michael H.} and Per Bakke and Amund Gulsvik and Lomas, {David A.} and Wayne Anderson and Xiangyang Kong and Rennard, {Stephen Israel} and Beaty, {Terri H.} and Hokanson, {John E.} and Crapo, {James D.} and Silverman, {Edwin K.} and Harvey Coxson and Lisa Edwards and Katharine Knobil and William MacNee and Ruth Tal-Singer and J{\o}rgen Vestbo and Julie Yates and Jeffrey Curtis and Ella Kazerooni and Nicola Hanania and Philip Alapat and Venkata Bandi and Kalpalatha Guntupalli and Elizabeth Guy and Antara Mallampalli and Charles Trinh and Mustafa Atik and Dawn DeMeo and Craig Hersh and George Washko and Francine Jacobson and Graham Barr and Byron Thomashow and John Austin and Neil MacIntyre and Lacey Washington and McAdams, {H. Page} and Richard Rosiello and Timothy Bresnahan and Charlene McEvoy and Joseph Tashjian and Robert Wise and Nadia Hansel and Robert Brown and Gregory Diette and Richard Casaburi and Janos Porszasz and Hans Fischer and Matt Budoff and Amir Sharafkhaneh and Hirani Kamal and Roham Darvishi and Dennis Niewoehner and Tadashi Allen and Quentin Anderson and Kathryn Rice and Marilyn Foreman and Gloria Westney and Eugene Berkowitz and Russell Bowler and Adam Friedlander and David Lynch and Joyce Schroeder and John Newell and Gerard Criner and Victor Kim and Nathaniel Marchetti and Aditi Satti and Mamary, {A. James} and Robert Steiner and Chandra Dass and William Bailey and Mark Dransfield and Hrudaya Nath and Joe Ramsdell and Paul Friedman and Geoffrey McLennan and {Van Beek}, {Edwin J.R.} and Brad Thompson and Dwight Look and Fernando Martinez and Han, {Mei Lan} and Christine Wendt and Frank Sciurba and Joel Weissfeld and Carl Fuhrman and Jessica Bon and Antonio Anzueto and Sandra Adams and Carlos Orozco and Mario Ruiz",
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T1 - Genome-wide association study of smoking behaviours in patients with COPD

AU - Siedlinski, Mateusz

AU - Cho, Michael H.

AU - Bakke, Per

AU - Gulsvik, Amund

AU - Lomas, David A.

AU - Anderson, Wayne

AU - Kong, Xiangyang

AU - Rennard, Stephen Israel

AU - Beaty, Terri H.

AU - Hokanson, John E.

AU - Crapo, James D.

AU - Silverman, Edwin K.

AU - Coxson, Harvey

AU - Edwards, Lisa

AU - Knobil, Katharine

AU - MacNee, William

AU - Tal-Singer, Ruth

AU - Vestbo, Jørgen

AU - Yates, Julie

AU - Curtis, Jeffrey

AU - Kazerooni, Ella

AU - Hanania, Nicola

AU - Alapat, Philip

AU - Bandi, Venkata

AU - Guntupalli, Kalpalatha

AU - Guy, Elizabeth

AU - Mallampalli, Antara

AU - Trinh, Charles

AU - Atik, Mustafa

AU - DeMeo, Dawn

AU - Hersh, Craig

AU - Washko, George

AU - Jacobson, Francine

AU - Barr, Graham

AU - Thomashow, Byron

AU - Austin, John

AU - MacIntyre, Neil

AU - Washington, Lacey

AU - McAdams, H. Page

AU - Rosiello, Richard

AU - Bresnahan, Timothy

AU - McEvoy, Charlene

AU - Tashjian, Joseph

AU - Wise, Robert

AU - Hansel, Nadia

AU - Brown, Robert

AU - Diette, Gregory

AU - Casaburi, Richard

AU - Porszasz, Janos

AU - Fischer, Hans

AU - Budoff, Matt

AU - Sharafkhaneh, Amir

AU - Kamal, Hirani

AU - Darvishi, Roham

AU - Niewoehner, Dennis

AU - Allen, Tadashi

AU - Anderson, Quentin

AU - Rice, Kathryn

AU - Foreman, Marilyn

AU - Westney, Gloria

AU - Berkowitz, Eugene

AU - Bowler, Russell

AU - Friedlander, Adam

AU - Lynch, David

AU - Schroeder, Joyce

AU - Newell, John

AU - Criner, Gerard

AU - Kim, Victor

AU - Marchetti, Nathaniel

AU - Satti, Aditi

AU - Mamary, A. James

AU - Steiner, Robert

AU - Dass, Chandra

AU - Bailey, William

AU - Dransfield, Mark

AU - Nath, Hrudaya

AU - Ramsdell, Joe

AU - Friedman, Paul

AU - McLennan, Geoffrey

AU - Van Beek, Edwin J.R.

AU - Thompson, Brad

AU - Look, Dwight

AU - Martinez, Fernando

AU - Han, Mei Lan

AU - Wendt, Christine

AU - Sciurba, Frank

AU - Weissfeld, Joel

AU - Fuhrman, Carl

AU - Bon, Jessica

AU - Anzueto, Antonio

AU - Adams, Sandra

AU - Orozco, Carlos

AU - Ruiz, Mario

PY - 2011/1/1

Y1 - 2011/1/1

N2 - 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.

AB - 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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