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Beyond cigarettes per day. A genome-wide association study of the biomarker carbon monoxide.

ABSTRACT: 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 (? = 2.66; 95% confidence interval [CI], 1.74-3.58; P = 1.65 × 10(-8)), and this association remains strong after adjusting for smoking behavior (? = 2.18; 95% CI, 1.32-3.04; P = 7.47 × 10(-7)). The correlation between CO and cigarettes per day is statistically significantly lower (z = 3.43; P = 6.07 × 10(-4)) 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.

SUBMITTER: Bloom AJ

PROVIDER: S-EPMC4214060 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Beyond cigarettes per day. A genome-wide association study of the biomarker carbon monoxide.

Bloom A Joseph AJ Hartz Sarah M SM Baker Timothy B TB Chen Li-Shiun LS Piper Megan E ME Fox Louis L Martinez Maribel M Hatsukami Dorothy D Johnson Eric O EO Laurie Cathy C CC Saccone Nancy L NL Goate Alison A Bierut Laura J LJ

Annals of the American Thoracic Society 20140901 7

<h4>Rationale</h4>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.<h4>Objectives</h4>To compare the g ...[more]

PMID: 25072098

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Project description:IntroductionTo examine whether changes in select measures of e-cigarette puffing topography are associated with changes in smoking behavior.MethodsSixteen current cigarette smokers were instructed to completely switch from smoking combustible cigarettes to using e-cigarettes over a 2-week period. The study was completed in the Southern Midwestern region of the United States. Measures included demographics, smoking history, and cigarette dependence, as well as baseline and 2-week follow-up self-reported cigarettes per day, cigarette craving and urges, exhaled carbon monoxide readings, and e-cigarette usage data (puff number, puffing time, and average puff duration) collected via the e-cigarette built-in puff counter.ResultsOver the 2-week switching period, participants significantly reduced their cigarettes per day (~80% reduction, p < .0001). Although the number of e-cigarette puffs/day remained relatively stable (p > .05), the average total e-cigarette daily puffing time increased significantly (p = .001). Users' average puff duration increased by 91 ms/puff/d (p < .001). The percentage decrease in cigarettes smoked per day was significantly and directly related to the slope of subjects' average puff duration over time (r(13) = .62, p = .01), such that as cigarettes per day decreased, puff duration increased. Self-reported smoking urges remained relatively stable from baseline to the end of the 2-week period (p > .05).ConclusionsAmong smokers switching to an e-cigarette, greater increases in e-cigarette puff duration was associated with greater reductions in cigarette smoking.ImplicationsThe current study is one of the first to examine changes in smokers' e-cigarette puffing behavior and associated changes in cigarette consumption as they attempt to completely switch to e-cigarettes. During a 2-week switching period, participants reduced their cigarettes per day. Moreover, although e-cigarette puffs per day remained relatively stable, users' average puff duration increased significantly. Greater increases in e-cigarette puff duration were associated with greater reductions in cigarette smoking. Understanding how to effectively use an e-cigarette to best reduce and eventually quit smoking will be necessary as smokers increasingly turn to these products to facilitate possible cessation.

Project description:IntroductionCigarette smoking is a major environmental risk factor for many diseases, including chronic obstructive pulmonary disease (COPD). There are shared genetic influences on cigarette smoking and COPD. Genetic risk factors for cigarette smoking in cohorts enriched for COPD are largely unknown.MethodsWe performed genome-wide association analyses for average cigarettes per day (CPD) across the Genetic Epidemiology of COPD (COPDGene) non-Hispanic white (NHW) (n = 6659) and African American (AA) (n = 3260), GenKOLS (the Genetics of Chronic Obstructive Lung Disease) (n = 1671), and ECLIPSE (the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) (n = 1942) cohorts. In addition, we performed exome array association analyses across the COPDGene NHW and AA cohorts. We considered analyses across the entire cohort and stratified by COPD case-control status.ResultsWe identified genome-wide significant associations for CPD on chromosome 15q25 across all cohorts (lowest p = 1.78 × 10-15), except in the COPDGene AA cohort alone. Previously reported associations on chromosome 19 had suggestive and directionally consistent associations (RAB4, p = 1.95 × 10-6; CYP2A7, p = 7.50 × 10-5; CYP2B6, p = 4.04 × 10-4). When we stratified by COPD case-control status, single nucleotide polymorphisms on chromosome 15q25 were nominally associated with both NHW COPD cases (β = 0.11, p = 5.58 × 10-4) and controls (β = 0.12, p = 3.86 × 10-5) For the gene-based exome array association analysis of rare variants, there were no exome-wide significant associations. For these previously replicated associations, the most significant results were among COPDGene NHW subjects for CYP2A7 (p = 5.2 × 10-4).ConclusionsIn a large genome-wide association study of both common variants and a gene-based association of rare coding variants in ever-smokers, we found genome-wide significant associations on chromosome 15q25 with CPD for common variants, but not for rare coding variants. These results were directionally consistent among COPD cases and controls.ImplicationsWe examined both common and rare coding variants associated with CPD in a large population of heavy smokers with and without COPD of NHW and AA descent. We replicated genome-wide significant associations on chromosome 15q25 with CPD for common variants among NHW subjects, but not for rare variants. We demonstrated for the first time that common variants on chromosome 15q25 associated with CPD are similar among COPD cases and controls. Previously reported associations on chromosome 19 showed suggestive and directionally consistent associations among common variants (RAB4, CYP2A7, and CYP2B6) and for rare variants (CYP2A7) among COPDGene NHW subjects. Although the genetic effect sizes for these single nucleotide polymorphisms on chromosome 15q25 are modest, we show that this creates a substantial smoking burden over the lifetime of a smoker.

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Beyond cigarettes per day. A genome-wide association study of the biomarker carbon monoxide.

Publications

Beyond cigarettes per day. A genome-wide association study of the biomarker carbon monoxide.

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