Dataset Information

CHRNB3 is more strongly associated with Fagerstrom test for cigarette dependence-based nicotine dependence than cigarettes per day: phenotype definition changes genome-wide association studies results.

ABSTRACT: AIMS:Nicotine dependence is a highly heritable disorder associated with severe medical morbidity and mortality. Recent meta-analyses have found novel genetic loci associated with cigarettes per day (CPD), a proxy for nicotine dependence. The aim of this paper is to evaluate the importance of phenotype definition (i.e., CPD versus Fagerström test for cigarette dependence (FTCD) score as a measure of nicotine dependence) on genome-wide association studies of nicotine dependence. DESIGN:Genome-wide association study. SETTING:Community sample. PARTICIPANTS:A total of 3365 subjects who had smoked at least one cigarette were selected from the Study of Addiction: Genetics and Environment (SAGE). Of the participants, 2267 were European Americans, 999 were African Americans. MEASUREMENTS:Nicotine dependence defined by FTCD score ?4, CPD. FINDINGS:The genetic locus most strongly associated with nicotine dependence was rs1451240 on chromosome 8 in the region of CHRNB3 [odds ratio (OR)?=?0.65, P?=?2.4?×?10(-8) ]. This association was further strengthened in a meta-analysis with a previously published data set (combined P?=?6.7?×?10(-16) , total n?=?4200). When CPD was used as an alternate phenotype, the association no longer reached genome-wide significance (? ?= ?-0.08, P?=?0.0004). CONCLUSIONS:Daily cigarette consumption and the Fagerstrom Test for Cigarette Dependence show different associations with polymorphisms in genetic loci.

SUBMITTER: Rice JP

PROVIDER: S-EPMC3427406 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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CHRNB3 is more strongly associated with Fagerström test for cigarette dependence-based nicotine dependence than cigarettes per day: phenotype definition changes genome-wide association studies results.

Rice John P JP Hartz Sarah M SM Agrawal Arpana A Almasy Laura L Bennett Siiri S Breslau Naomi N Bucholz Kathleen K KK Doheny Kimberly F KF Edenberg Howard J HJ Goate Alison M AM Hesselbrock Victor V Howells William B WB Johnson Eric O EO Kramer John J Krueger Robert F RF Kuperman Samuel S Laurie Cathy C Manolio Teri A TA Neuman Rosalind J RJ Nurnberger John I JI Porjesz Bernice B Pugh Elizabeth E Ramos Erin M EM Saccone Nancy N Saccone Scott S Schuckit Marc M Bierut Laura J LJ

Addiction (Abingdon, England) 20120615 11

<h4>Aims</h4>Nicotine dependence is a highly heritable disorder associated with severe medical morbidity and mortality. Recent meta-analyses have found novel genetic loci associated with cigarettes per day (CPD), a proxy for nicotine dependence. The aim of this paper is to evaluate the importance of phenotype definition (i.e., CPD versus Fagerström test for cigarette dependence (FTCD) score as a measure of nicotine dependence) on genome-wide association studies of nicotine dependence.<h4>Design< ...[more]

PMID: 22524403

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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:BackgroundMany smokers report attempting to quit each year, yet most relapse, in part due to exposure to smoking-related cues. It is hypothesized that extinction of the cue-drug association could be facilitated through random nicotine delivery (RND), thus making it easier for smokers to quit. The current study aimed to evaluate the effects of RND on smoking cessation-related outcomes including cigarettes per day (CPD) and exhaled carbon monoxide (CO).MethodsParticipants were current smokers (>9 CPD) interested in quitting. Novel trans-mucosal, orally dissolving nicotine films, developed by Bionex Pharmaceuticals, were used in the study. The pharmacokinetic profile of these films was assessed in single (Experiment 1) and multiple-dose (Experiment 2) administrations prior to the smoking cessation study (Experiment 3). In Experiment 3, participants were randomized 1:1:1 to recieve 4 nicotine films per day of either: placebo delivery (0 mg), steady-state delivery (2 mg), or random nicotine delivery (RND) (0 mg or 4 mg). After two weeks, participants were advised to quit (target quit date, TQD) and were followed up 4 weeks later to collect CPD and CO and to measure dependence (Penn State Cigarette Dependence Index; PSCDI) and craving (Questionnaire of Smoking Urges; QSU-Brief). Means and frequencies were used to describe the data and repeated measures ANOVA was used to determine differences between groups.ResultsThe pharmacokinetic studies (Experiment 1 and 2) demonstrated that the films designed for this study delivered nicotine as expected, with the 4 mg film delivering a nicotine boost of approximately 12.4 ng/mL across both the single and the multiple dose administration studies. The films reduced craving for a cigarette and were well-tolerated, overall, and caused no changes in blood pressure or heart rate. Using these films in the cessation study (Experiment 3) (n = 45), there was a significant overall reduction in cigarettes smoked per day (CPD) and in exhaled CO, with no significant differences across groups (placebo, steady-state, RND). In addition, there were no group differences in dependence or craving. Adverse events included heartburn, hiccups, nausea, and to a lesser extent, vomiting and anxiety and there were no differences across groups.ConclusionOverall, this pilot study found that RND via orally dissolving films was feasible and well tolerated by participants. However, RND participants did not experience a greater reduction in self-reported CPD and exhaled CO, compared with participants in the steady-state and placebo delivery groups. Future studies to evaluate optimal RND parameters with larger sample sizes are needed to fully understand the effect of RND on smoking cessation-related outcomes.

Dataset Information

CHRNB3 is more strongly associated with Fagerstrom test for cigarette dependence-based nicotine dependence than cigarettes per day: phenotype definition changes genome-wide association studies results.

Publications

CHRNB3 is more strongly associated with Fagerström test for cigarette dependence-based nicotine dependence than cigarettes per day: phenotype definition changes genome-wide association studies results.

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