Association of genetic liability to smoking initiation with e-cigarette use in young adults

Background Smoking and e-cigarette use are strongly associated, but it is currently unclear whether this association is causal, or due to shared factors that influence both behaviours such as a shared genetic liability. The aim of this study was to investigate whether polygenic risk scores (PRS) for smoking initiation are associated with ever use of e-cigarettes. Methods and Findings PRS of smoking initiation were calculated for young adults (aged 23 to 26 years) of European ancestry in the Avon Longitudinal Study of Parents and Children using the GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN) summary statistics. Five thresholds ranging from 5×10 −8 to 0.5 were used to calculate five PRS for each individual. Using logistic regression, we investigated the association between smoking initiation PRS and both self-reported smoking initiation and self-reported e-cigarette use, as well as a number of negative control outcomes (socioeconomic position at birth, externalising disorders in childhood and risk-taking in young adulthood). We observed positive associations of similar magnitude between smoking initiation PRS and both smoking initiation (OR = 1.29, 95% CI 1.19 to 1.39) and ever e-cigarette use (OR = 1.24, 95% CI 1.14 to 1.34) by the age of 24 years. At lower p -value thresholds, we observed an association between smoking initiation PRS and ever e-cigarette use among never smokers. We also found evidence of associations between smoking initiation PRS and some negative control outcomes, particularly when less stringent p -value thresholds were used but also at the strictest threshold (e.g., gambling, number of sexual partners, conduct disorder at 7 years, and parental socioeconomic position at birth). Conclusions Our results indicate that there may be a shared genetic aetiology between smoking and e-cigarette use, and also with socioeconomic position, externalising disorders in childhood, and risky behaviour more generally. Taken together, this indicates that there may be a common genetic vulnerability to both smoking and e-cigarette use, which may reflect a broad risk-taking phenotype.