Investigating the Impact of Genetics on the Effectiveness of Bupropion and Varenicline Treatment for Smoking Cessation

Abstract

Genetics plays a significant role in smoking behaviours and abstinence. In this genetics sub-study,we evaluated treatment-seeking Caucasian smokers (n =374) receiving bupropion (n = 180) or varenicline (n = 194) for smoking cessation. Genetic variants involved in nicotine neurobiology (CHRNA4, CHRNA5, CHRNB4 ) and the dopamine reward pathway (DRD2, SLC6A3 ) displayed nominal associations with abstinence. Additionally, DRD2 and COMT variants were nominally associated with cigarettes per day and nicotine dependence in the whole sample (n =374). However, genome-wide variants showed no significant associations with abstinence, or baseline smoking behaviours. Polygenic risk scores for smoking cessation (current versus former smoker) derived from the GWAS and Sequencing Consortium of Alcohol and Nicotine Use (GSCAN) meta-analysis sample, significantly predicted abstinence at the end of treatment and explained 2.188% of the variance for abstinence. These findings highlight the influence of genetic variants on smoking and the potential for personalized cessation strategies.