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

Jasmine N. Khouja; Robyn E. Wootton; Amy E. Taylor; George Davey Smith; Marcus R. Munafò

doi:10.1371/JOURNAL.PMED.1003555

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

Jasmine N. Khouja
, Robyn E. Wootton
, Amy E. Taylor
, George Davey Smith
, Marcus R. Munafò

Vice Chancellor's Office

University of Bristol
University Hospitals Bristol NHS Foundation Trust

Research output: Contribution to journal › Article › peer-review

38 Citations (SciVal)

Abstract

Background: 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.

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. 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 language	English
Article number	e1003555
Journal	PLoS Medicine
Volume	18
Issue number	3
Early online date	18 Mar 2021
DOIs	https://doi.org/10.1371/JOURNAL.PMED.1003555
Publication status	Published - 18 Mar 2021

Data Availability Statement

The data used in this study are available on request to the ALSPAC Executive ([email protected]). The ALSPAC data management plan describes in detail the policy regarding data sharing. Full instructions for applying for data access can be found here: http://www.bristol.ac.uk/alspac/researchers/access/. The ALSPAC study website contains details of all the data that are available (http://www.bristol.ac.uk/alspac/researchers/our-data/).

Acknowledgements

We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses.

The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, or the Department of Health and Social Care.

Funding

All authors are members of the Integrative Epidemiology Unit at the University of Bristol which is funded by the UK Medical Research Council (https://mrc.ukri.org/; grant numbers MC_UU_0001/1&7). The UK Medical Research Council and Wellcome (grant number 102215/2/13/2) and the University of Bristol (http://www.bristol.ac.uk/) provide core support for the Avon Longitudinal Study of Parents and Children (ALSPAC). A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). This research was specifically funded by a Cancer Research UK (https://www.cancerresearchuk.org/) grant to AET (grant number C54841/A20491). This publication is the work of the authors (JNK, REW, AET, GDS and MRM) who will serve as guarantors for the contents of this paper. AET and MRM are also supported by the NIHR Bristol Biomedical Research Centre (https://www.bristolbrc.nihr.ac.uk/) at University Hospitals Bristol NHS Foundation Trust and the University of Bristol. The sponsors played no role in the study design, data collection, data analysis, decision to publish, or preparation of the manuscript.

ASJC Scopus subject areas

General Medicine

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Cite this

@article{b1d5aafc706d495aaad4df096867fca9,

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

abstract = "Background: 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. 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. 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.",

author = "Khouja, \{Jasmine N.\} and Wootton, \{Robyn E.\} and Taylor, \{Amy E.\} and Smith, \{George Davey\} and Munaf{\`o}, \{Marcus R.\}",

year = "2021",

month = mar,

day = "18",

doi = "10.1371/JOURNAL.PMED.1003555",

language = "English",

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journal = "PLoS Medicine",

issn = "1549-1277",

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TY - JOUR

T1 - Association of genetic liability to smoking initiation with e-cigarette use in young adults

T2 - A cohort study

AU - Khouja, Jasmine N.

AU - Wootton, Robyn E.

AU - Taylor, Amy E.

AU - Smith, George Davey

AU - Munafò, Marcus R.

PY - 2021/3/18

Y1 - 2021/3/18

N2 - Background: 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. 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. 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.

AB - Background: 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. 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. 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.

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DO - 10.1371/JOURNAL.PMED.1003555

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AN - SCOPUS:85103230661

SN - 1549-1277

VL - 18

JO - PLoS Medicine

JF - PLoS Medicine

IS - 3

M1 - e1003555

ER -

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

Abstract

Data Availability Statement

Acknowledgements

Funding

ASJC Scopus subject areas

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