Genetic Prediction of Smoking Cessation Medication Side Effects: A Genome-Wide Investigation of Abnormal Dreams on Varenicline.

Varenicline, the most efficacious smoking cessation monotherapy, produces abnormal dreams. Although genetic contributions to varenicline-associated nausea and cessation have been identified, the role of genetics in abnormal dreams is unknown. We conducted a genomewide association study (GWAS) of abnormal dreams in 188 European ancestry smokers treated with varenicline (NCT01314001). Additive genetic models examined the likelihood of experiencing abnormal dreams 2 weeks following varenicline initiation. For the top locus, we tested for selectivity to varenicline, effects on cessation, replication, and generalizability to African ancestry (AA) individuals. The top GWAS variant associated with abnormal dreams was rs901886, mapping to intron 2 of ICAM5 on chromosome 19. The prevalence of abnormal dreams in those with rs901886 CC, CT, and TT genotypes was 15%, 36%, and 62%, respectively (odds ratio = 2.94 for T vs. C, 95% confidence interval = 1.92-4.55, P = 2.03e-7; T allele frequency = 52%). This rs901886 association was selective to varenicline (P values > 0.05 on nicotine patch and placebo). There were also positive associations for rs901886 T (vs. C allele, P = 0.03) and for abnormal dreams (P = 0.06) with varenicline-aided cessation. Neither rs901886 (P = 0.40) nor abnormal dreams (P = 0.24) were associated with adherence. A similar direction of effect of rs901886 on abnormal dreams was observed in a second varenicline trial (NCT01836276). In AA individuals (n = 137), rs901886 was not associated with abnormal dreams (P = 0.41), but there was an association for a variant located ~ 74.4 kb 5' of ICAM5 (P = 2.56e-3). Variation in ICAM5 may influence abnormal dreams and cessation on varenicline. These findings provide additional support for genetically optimized smoking cessation approaches.

Relationship Between Tobacco Product Use and Health-Related Quality of Life Among Individuals With COPD in Waves 1-5 (2013-2019) of the Population Assessment of Tobacco and Health Study.

Introduction: We examined the association between tobacco product use and health-related quality of life (HRQoL) among individuals with chronic obstructive pulmonary disease (COPD) in Waves 1-5 of the Population Assessment of Tobacco and Health (PATH) Study. Methods: Adults ≥40 years with an ever COPD diagnosis were included in cross-sectional (Wave 5) and longitudinal (Waves 1 to 5) analyses. Tobacco use included 13 mutually exclusive categories of past 30-day (P30D) single use and polyuse with P30D exclusive cigarette use and ≥5-year cigarette cessation as reference groups. Multivariable linear regression and generalized estimating equations (GEE) were used to examine the association between tobacco use and HRQoL as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) Global-10 questionnaire. Results: Of 1670 adults, 79.4% ever used cigarettes; mean (standard error [SE]) pack years was 30.9 (1.1). In cross-sectional analysis, P30D exclusive cigarette use, and e-cigarette/cigarette dual use were associated with worse HRQoL compared to ≥5-year cigarette cessation. Compared to P30D exclusive cigarette use, never tobacco use and ≥5-year cigarette cessation were associated with better HRQoL, while e-cigarette/cigarette dual use had worse HRQoL. Longitudinally (n=686), e-cigarette/cigarette dual use was associated with worsening HRQoL compared to both reference groups. Only never tobacco use was associated with higher HRQoL over time compared to P30D exclusive cigarette use. Conclusions: E-cigarette/cigarette dual use was associated with worse HRQoL compared to ≥5-year cigarette cessation and exclusive cigarette use. Never use and ≥5-year cigarette cessation were the only categories associated with higher HRQoL compared to exclusive cigarette use. Findings highlight the importance of complete smoking cessation for individuals with COPD.