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Deep sequencing of candidate genes identified 14 variants associated with smoking abstinence in an ethnically diverse sample.

ABSTRACT: Despite the large public health toll of smoking, genetic studies of smoking cessation have been limited with few discoveries of risk or protective loci. We investigated common and rare variant associations with success in quitting smoking using a cohort from 8 randomized controlled trials involving 2231 participants and a total of 10,020 common and 24,147 rare variants. We identified 14 novel markers including 6 mapping to genes previously related to psychiatric and substance use disorders, 4 of which were protective (CYP2B6 (rs1175607105), HTR3B (rs1413172952; rs1204720503), rs80210037 on chr15), and 2 of which were associated with reduced cessation (PARP15 (rs2173763), SCL18A2 (rs363222)). The others mapped to areas associated with cancer including FOXP1 (rs1288980) and ZEB1 (rs7349). Network analysis identified significant canonical pathways for the serotonin receptor signaling pathway, nicotine and bupropion metabolism, and several related to tumor suppression. Two novel markers (rs6749438; rs6718083) on chr2 are flanked by genes associated with regulation of bodyweight. The identification of novel loci in this study can provide new targets of pharmacotherapy and inform efforts to develop personalized treatments based on genetic profiles.

SUBMITTER: Cinciripini PM

PROVIDER: S-EPMC10944542 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Deep sequencing of candidate genes identified 14 variants associated with smoking abstinence in an ethnically diverse sample.

Cinciripini Paul M PM Wetter David W DW Wang Jian J Yu Robert R Kypriotakis George G Kumar Tapsi T Robinson Jason D JD Cui Yong Y Green Charles E CE Bergen Andrew W AW Kosten Thomas R TR Scherer Steven E SE Shete Sanjay S

Scientific reports 20240316 1

Despite the large public health toll of smoking, genetic studies of smoking cessation have been limited with few discoveries of risk or protective loci. We investigated common and rare variant associations with success in quitting smoking using a cohort from 8 randomized controlled trials involving 2231 participants and a total of 10,020 common and 24,147 rare variants. We identified 14 novel markers including 6 mapping to genes previously related to psychiatric and substance use disorders, 4 of ...[more]

PMID: 38493193

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Project description:ImportanceMillions of Americans are forced to quit smoking as they enter tobacco-free prisons and jails, but most return to smoking within days of release. Interventions are needed to sustain tobacco abstinence after release from incarceration.ObjectiveTo evaluate the extent to which the WISE intervention (Working Inside for Smoking Elimination), based on motivational interviewing (MI) and cognitive behavioral therapy (CBT), decreases relapse to smoking after release from a smoke-free prison.DesignParticipants were recruited approximately 8 weeks prior to their release from a smoke-free prison and randomized to 6 weekly sessions of either education videos (control) or the WISE intervention.SettingA tobacco-free prison in the United States.ParticipantsA total of 262 inmates (35% female).Main outcome measureContinued smoking abstinence was defined as 7-day point-prevalence abstinence validated by urine cotinine measurement.ResultsAt the 3-week follow-up, 25% of participants in the WISE intervention (31 of 122) and 7% of the control participants (9 of 125) continued to be tobacco abstinent (odds ratio [OR], 4.4; 95% CI, 2.0-9.7). In addition to the intervention, Hispanic ethnicity, a plan to remain abstinent, and being incarcerated for more than 6 months were all associated with increased likelihood of remaining abstinent. In the logistic regression analysis, participants randomized to the WISE intervention were 6.6 times more likely to remain tobacco abstinent at the 3-week follow up than those randomized to the control condition (95% CI, 2.5-17.0). Nonsmokers at the 3-week follow-up had an additional follow-up 3 months after release, and overall 12% of the participants in the WISE intervention (14 of 122) and 2% of the control participants (3 of 125) were tobacco free at 3 months, as confirmed by urine cotinine measurement (OR, 5.3; 95% CI, 1.4-23.8).Conclusions and relevanceForced tobacco abstinence alone during incarceration has little impact on postrelease smoking status. A behavioral intervention provided prior to release greatly improves cotinine-confirmed smoking cessation in the community.Trial registrationclinicaltrials.gov Identifier: NCT01122589.

Dataset Information

Deep sequencing of candidate genes identified 14 variants associated with smoking abstinence in an ethnically diverse sample.

Publications

Deep sequencing of candidate genes identified 14 variants associated with smoking abstinence in an ethnically diverse sample.

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