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 Curtis; 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

doi:10.1136/thoraxjnl-2011-200154

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

79 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 language	English (US)
Pages (from-to)	894-902
Number of pages	9
Journal	Thorax
Volume	66
Issue number	10
DOIs	https://doi.org/10.1136/thoraxjnl-2011-200154
State	Published - Oct 2011

ASJC Scopus subject areas

Pulmonary and Respiratory Medicine

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10.1136/thoraxjnl-2011-200154

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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

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

@article{9bc1965076754f09b1f95e54109d2fb4,

title = "Genome-wide association study of smoking behaviours in patients with COPD",

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 I.} 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",

note = "Funding Information: This article is based on research that is funded in part by grants from the National Institute of Health (NIH) and is therefore subject to the mandatory NIH Public Access Policy. The final, peer-reviewed manuscript must be deposited with the PubMed Central (PMC) database upon acceptance for publication and be made publicly accessible no later than 12 months after publication. Funding Information: Funding This work was supported by US National Institutes of Health (NIH) grants R01 HL075478, R01 HL084323, P01 HL0830B9, U01 HL08985B (Silverman), K12HL089990 (Cho), and U01 HL089897 (Crapo) . The National Emphysema Treatment Trial was supported by the National Heart, Lung, and Blood Institute contracts ( N01HR76101, N01HR76102, N01HR76103, N01HR76104, N01HR76105, N01HR761 O6, N01HR76107, N01HR76108, N01HR76109, N01HR76110, N01HR76111, N01HR76112, N01HR76113, N01HR76114, N01HR76115, N01HR76116, N01HR76118, N01HR76119 ), the Centers for Medicare and Medicaid Services, and the Agency for Healthcare Research and Quality. The Norway cohort and the ECLIPSE study ( http://www.Clinicaltrials.gov identifier NCT00292552 ; GSK Code SCO104960) are funded by GlaxoSmithKline. The COPDGene project was supported by Award Number U01HL089897 and Award Number U01HL089856 from the National Heart, Lung, and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health. The COPDGene project is also supported by the COPD Foundation through contributions made to an Industry Advisory Board comprised of AstraZeneca, Pfizer, Boehrlnger Ingelhelm, Novartis and Sepracor. M. Siedlinski is a recipient of a post-doctoral fellowship from the Niels Stensen Foundation. ",

year = "2011",

month = oct,

doi = "10.1136/thoraxjnl-2011-200154",

language = "English (US)",

volume = "66",

pages = "894--902",

journal = "Thorax",

issn = "0040-6376",

publisher = "BMJ Publishing Group",

number = "10",

}

TY - JOUR

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 I.

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

N1 - Funding Information: This article is based on research that is funded in part by grants from the National Institute of Health (NIH) and is therefore subject to the mandatory NIH Public Access Policy. The final, peer-reviewed manuscript must be deposited with the PubMed Central (PMC) database upon acceptance for publication and be made publicly accessible no later than 12 months after publication. Funding Information: Funding This work was supported by US National Institutes of Health (NIH) grants R01 HL075478, R01 HL084323, P01 HL0830B9, U01 HL08985B (Silverman), K12HL089990 (Cho), and U01 HL089897 (Crapo) . The National Emphysema Treatment Trial was supported by the National Heart, Lung, and Blood Institute contracts ( N01HR76101, N01HR76102, N01HR76103, N01HR76104, N01HR76105, N01HR761 O6, N01HR76107, N01HR76108, N01HR76109, N01HR76110, N01HR76111, N01HR76112, N01HR76113, N01HR76114, N01HR76115, N01HR76116, N01HR76118, N01HR76119 ), the Centers for Medicare and Medicaid Services, and the Agency for Healthcare Research and Quality. The Norway cohort and the ECLIPSE study ( http://www.Clinicaltrials.gov identifier NCT00292552 ; GSK Code SCO104960) are funded by GlaxoSmithKline. The COPDGene project was supported by Award Number U01HL089897 and Award Number U01HL089856 from the National Heart, Lung, and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health. The COPDGene project is also supported by the COPD Foundation through contributions made to an Industry Advisory Board comprised of AstraZeneca, Pfizer, Boehrlnger Ingelhelm, Novartis and Sepracor. M. Siedlinski is a recipient of a post-doctoral fellowship from the Niels Stensen Foundation.

PY - 2011/10

Y1 - 2011/10

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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DO - 10.1136/thoraxjnl-2011-200154

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SP - 894

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JO - Thorax

JF - Thorax

IS - 10

ER -

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

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