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 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). Results 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.