Association of genetic liability to smoking initiation with e-cigarette use in young adults: A cohort study

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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.
Methods and Findings
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 five 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 eight 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 (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.
Original languageEnglish
Article numbere1003555
Pages (from-to)e1003555
Number of pages16
JournalPLoS Medicine
Issue number3
Publication statusPublished - 18 Mar 2021

Bibliographical note

Funding Information:
The data used in the empirical study of were collected as part of the Regional Program on Enterprise Development (RPED), organized by the World Bank. The project received support from the Swedish, Norwegian, United Kingdom, Canadian, and Dutch governments. The full data set was downloaded from the web site of the Centre for the Study of African Economies at the University of Oxford (CSAE): .

Publisher Copyright:
© 2021 Khouja et al.


  • E-cigarettes
  • Smoking
  • Polygenic risk score (PRS)


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