Abstract
Tobacco 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. Smoking initiation PRS were calculated for young adults (N = 7,859, mean age = 24 years, 51% male) of European ancestry in the Avon Longitudinal Study of Parents and Children, a prospective birth cohort study initiated in 1991. PRS were calculated 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 5 PRS for each individual. Using logistic regression, we investigated the association between smoking initiation PRS and the main outcome, self-reported e-cigarette use (n = 2,894, measured between 2016 and 2017), as well as self-reported smoking initiation and 8 negative control outcomes (socioeconomic position at birth, externalising disorders in childhood, and risk-taking in young adulthood). A total of 878 young adults (30%) had ever used e-cigarettes at 24 years, and 150 (5%) were regular e-cigarette users at 24 years. We observed positive associations of similar magnitude between smoking initiation PRS (created using the p < 5 × 10-8 threshold) and both smoking initiation (odds ratio (OR) = 1.29, 95% CI 1.19 to 1.39, p < 0.001) and ever e-cigarette use (OR = 1.24, 95% CI 1.14 to 1.34, p < 0.001) by the age of 24 years, indicating that a genetic predisposition to smoking initiation is associated with an increased risk of using e-cigarettes. 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 to create the PRS, but also at the strictest threshold (e.g., gambling, number of sexual partners, conduct disorder at 7 years, and parental socioeconomic position at birth). However, this study is limited by the relatively small sample size and potential for collider bias. 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. 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.
Highlights
There are an estimated 3.6 million electronic cigarette (e-cigarette) users in Great Britain [1], and evidence is growing that e-cigarettes are effective in helping tobacco smokers quit [2,3]
The exact definition varied across the cohorts included in the consortium, with 3 different definitions: (1) Have you smoked over 100 cigarettes over the course of your life? (2) Have you ever smoked every day for at least a month? (3) Have you ever smoked regularly? The majority of the single nucleotide polymorphism (SNP) identified were intergenic with no known function, but glutamate and dopaminergic gene pathways were enriched for smoking initiation
A total of 378 SNPs were identified as genome-wide significant in the GSCAN genome-wide association studies (GWAS) of smoking initiation [9], 356 of which were available in Avon Longitudinal Study of Parents and Children (ALSPAC)
Summary
There are an estimated 3.6 million electronic cigarette (e-cigarette) users in Great Britain [1], and evidence is growing that e-cigarettes are effective in helping tobacco smokers quit [2,3]. A recent meta-analysis found that for young people aged 30 years or younger, there is a strong and consistent positive association between ecigarette use among never smokers and later smoking, but that there is currently insufficient evidence to conclude that this association is causal [5]. Understanding more about the nature of the association between smoking and e-cigarette use, in young adulthood, is vital to inform tobacco control policies that aim to prevent youth smoking initiation by restricting access to e-cigarettes. It is important to understand whether the association found among young adults is causal, or due to other factors that influence both smoking and e-cigarette use independently. Tobacco 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
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