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

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

doi:10.1136/thoraxjnl-2011-200154

Cited by 101 publications

(94 citation statements)

References 41 publications

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“…However, it is also possible that these genetic loci influence smoking behaviors via separate mechanisms that differentially impact levels of CO versus number of cigarettes smoked per day (e.g., influencing responses to nicotine in the initiation of smoking behaviors versus promoting more intense smoking of individual cigarettes and increased tolerance to smoking's aversive effects) (41,42). The existence of separable mechanisms influencing levels of CO versus amount smoked is consistent with findings that the CHRNA6-CHRNB3 locus shows little contribution to the genetic risk of COPD and lung cancer in the large-scale studies (43,44).…”

Section: Original Researchsupporting

confidence: 68%

Beyond Cigarettes Per Day. A Genome-Wide Association Study of the Biomarker Carbon Monoxide

Bloom¹,

Hartz²,

Baker

et al. 2014

Annals ATS

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Rationale: The CHRNA5-CHRNA3-CHRNB4 locus is associated with self-reported smoking behavior and also harbors the strongest genetic associations with chronic obstructive pulmonary disease (COPD) and lung cancer. Because the associations with lung disease remain after adjustment for self-reported smoking behaviors, it has been asserted that CHRNA5-CHRNA3-CHRNB4 variants increase COPD and lung cancer susceptibility independently of their effects on smoking.Objectives: To compare the genetic associations of exhaled carbon monoxide (CO), a biomarker of current cigarette exposure, with self-reported smoking behaviors.Methods: A total of 1,521 European American and 247 African American current smokers recruited into smoking cessation studies were assessed for CO at intake before smoking cessation. DNA samples were genotyped using the Illumina Omni2.5 microarray. Genetic associations with CO and smoking behaviors (cigarettes smoked per day, Fagerstrom test for nicotine dependence) were studied. Measurements and Main Results:Variants in the CHRNA5-CHRNA3-CHRNB4 locus, including rs16969968, a nonsynonymous variant in CHRNA5, are genomewide association study-significantly associated with CO (b = 2.66; 95% confidence interval [CI], 1.74-3.58; P = 1.65 3 10 28 ), and this association remains strong after adjusting for smoking behavior (b = 2.18; 95% CI, 1.32-3.04; P = 7.47 3 10 27 ). The correlation between CO and cigarettes per day is statistically significantly lower (z = 3.43; P = 6.07 3 10 24 ) in African Americans (r = 0.14; 95% CI, 0.02-0.26; P = 0.003) than in European-Americans (r = 0.36; 95% CI, 0.31-0.40; P = 0.0001).Conclusions: Exhaled CO, a biomarker that is simple to measure, captures aspects of cigarette smoke exposure in current smokers beyond the number of cigarettes smoked per day. Behavioral measures of smoking are therefore insufficient indices of cigarette smoke exposure, suggesting that genetic associations with COPD or lung cancer that persist after adjusting for self-reported smoking behavior may still reflect genetic effects on smoking exposure.

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Section: Original Researchsupporting

confidence: 68%

Beyond Cigarettes Per Day. A Genome-Wide Association Study of the Biomarker Carbon Monoxide

Bloom¹,

Hartz²,

Baker

et al. 2014

Annals ATS

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“…25 The tobacco and genetics consortium did a meta-analysis totalling 74 053 subjects and found DBH rs3025343 [G] is associated with smoking cessation. 26 Siedlinski et al 27 reported the genome-wide study of chronic obstructive pulmonary disease. They could replicate the result by the above consortium; that is, there was an association between a candidate genotype rs3025343 and smoking cessation in their subjects.…”

Section: Discussionmentioning

confidence: 99%

Association between dopamine beta hydroxylase rs5320 polymorphism and smoking behaviour in elderly Japanese

et al. 2012

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The dopaminergic brain pathway is involved in many addictive behaviours, hence represents a good candidate in the study of smoking behaviour and nicotine addiction. Dopamine beta hydroxylase (DBH) is an enzyme that catalyses the conversion of dopamine into noradrenaline. This study, the first of its kind, was done to investigate the role of DBH rs5320 polymorphism in smoking behaviour of elderly Japanese. This was done by collecting blood samples from 2521 subjects with various smoking habits to genotype the DBH rs5320 polymorphism. Participants also had to fill out a questionnaire containing questions regarding their lifestyles. Some of the questions were from the Fagerströ m Test for Nicotine Dependence (FTND) and the Tobacco Dependence Screener (TDS). It was found that male ever-smokers with AA genotype smoked less cigarettes per day than those with GG and AG genotypes. FTND scores were also lowest in male ever-smokers with AA genotype and in female ever-smokers with AG genotype. There was no correlation detected between the TDS scores and any of the genotypes. This study shows that DBH rs5320 polymorphism influences nicotine dependence.

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“…[P ¼ 0.03, minor allele frequency (MAF) ¼ 0.04, imputation r 2 0.3-0.4 using HapMap2 data] previously described in this cohort as associated with lifetime average cigarettes per day (26), and rs36012476 in ADCK4 (P ¼ 0.02, MAF ¼ 0.07, and imputation r 2 0.6-0.7). Inclusion of these SNPs only modestly attenuated the signal for rs7937 (P after adjustment ¼ 8.3 × 10 28 ).…”

Section: Resultsmentioning

confidence: 99%

A Genome-Wide Association Study In COPD Identifies A Susceptibility Locus On Chromosome 19q13

Cho

Castaldi

Hersh

et al. 2011

A95. Cutting Edge Insights to the Pathobiology of Copd and Interstitial Lung Disease

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The genetic risk factors for chronic obstructive pulmonary disease (COPD) are still largely unknown. To date, genome-wide association studies (GWASs) of limited size have identified several novel risk loci for COPD at CHRNA3/CHRNA5/IREB2, HHIP and FAM13A; additional loci may be identified through larger studies. We performed a GWAS using a total of 3499 cases and 1922 control subjects from four cohorts: the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); the Normative Aging Study (NAS) and National Emphysema Treatment Trial (NETT); Bergen, Norway (GenKOLS); and the COPDGene study. Genotyping was performed on Illumina platforms with additional markers imputed using 1000 Genomes data; results were summarized using fixed-effect meta-analysis. We identified a new genomewide significant locus on chromosome 19q13 (rs7937, OR 5 0.74, P 5 2.9 3 10 29 ). Genotyping this single * Molecular Genetics, 2012, Vol. 21, No. 4 947-957 doi:10.1093/hmg/ddr524 Advance Access published on November 11, 2011nucleotide polymorphism (SNP) and another nearby SNP in linkage disequilibrium (rs2604894) in 2859 subjects from the family-based International COPD Genetics Network study (ICGN) demonstrated supportive evidence for association for COPD (P 5 0.28 and 0.11 for rs7937 and rs2604894), pre-bronchodilator FEV 1 (P 5 0.08 and 0.04) and severe (GOLD 3&4) COPD (P 5 0.09 and 0.017). This region includes RAB4B, EGLN2, MIA and CYP2A6, and has previously been identified in association with cigarette smoking behavior.

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

Cited by 101 publications

References 41 publications

Beyond Cigarettes Per Day. A Genome-Wide Association Study of the Biomarker Carbon Monoxide

Beyond Cigarettes Per Day. A Genome-Wide Association Study of the Biomarker Carbon Monoxide

Association between dopamine beta hydroxylase rs5320 polymorphism and smoking behaviour in elderly Japanese

A Genome-Wide Association Study In COPD Identifies A Susceptibility Locus On Chromosome 19q13

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