{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T04:57:29Z","timestamp":1792990649993,"version":"4.5.0"},"reference-count":28,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T00:00:00Z","timestamp":1616025600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_0001\/1&7"],"award-info":[{"award-number":["MC_UU_0001\/1&7"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["102215\/2\/13\/2"],"award-info":[{"award-number":["102215\/2\/13\/2"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["102215\/2\/13\/2"],"award-info":[{"award-number":["102215\/2\/13\/2"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C54841\/A20491"],"award-info":[{"award-number":["C54841\/A20491"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015250","name":"NIHR Bristol Biomedical Research Centre","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015250","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100015250","name":"NIHR Bristol Biomedical Research Centre","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015250","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and findings<\/jats:title>\n                    <jats:p>\n                      Smoking initiation PRS were calculated for young adults (\n                      <jats:italic>N<\/jats:italic>\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 &amp; Sequencing Consortium of Alcohol and Nicotine use (GSCAN) summary statistics. Five thresholds ranging from 5 \u00d7 10\n                      <jats:sup>\u22128<\/jats:sup>\n                      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                      <jats:italic>n =<\/jats:italic>\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\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 5 \u00d7 10\n                      <jats:sup>\u22128<\/jats:sup>\n                      threshold) and both smoking initiation (odds ratio (OR) = 1.29, 95% CI 1.19 to 1.39,\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001) and ever e-cigarette use (OR = 1.24, 95% CI 1.14 to 1.34,\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 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\n                      <jats:italic>p<\/jats:italic>\n                      -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\n                      <jats:italic>p<\/jats:italic>\n                      -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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pmed.1003555","type":"journal-article","created":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T13:27:37Z","timestamp":1616074057000},"page":"e1003555","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":52,"title":["Association of genetic liability to smoking initiation with e-cigarette use in young adults: A cohort study"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7944-2981","authenticated-orcid":true,"given":"Jasmine N.","family":"Khouja","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3961-3202","authenticated-orcid":true,"given":"Robyn E.","family":"Wootton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy E.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1407-8314","authenticated-orcid":true,"given":"George","family":"Davey Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4049-993X","authenticated-orcid":true,"given":"Marcus R.","family":"Munaf\u00f2","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,3,18]]},"reference":[{"key":"pmed.1003555.ref001","volume-title":"Use of e-cigarettes (vapourisers) among adults in Great Britain","author":"Action on Smoking and Health","year":"2019"},{"issue":"7","key":"pmed.1003555.ref002","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1056\/NEJMoa1808779","article-title":"A Randomized Trial of E-Cigarettes versus Nicotine-Replacement Therapy","volume":"380","author":"P Hajek","year":"2019","journal-title":"N Engl J Med"},{"issue":"i4645","key":"pmed.1003555.ref003","article-title":"Association between electronic cigarette use and changes in quit attempts, success of quit attempts, use of smoking cessation pharmacotherapy, and use of stop smoking services in England: time series analysis of population trends","volume":"354","author":"E Beard","year":"2016","journal-title":"BMJ"},{"key":"pmed.1003555.ref004","doi-asserted-by":"crossref","first-page":"108362","DOI":"10.1016\/j.drugalcdep.2020.108362","article-title":"Associations between reasons for vaping and current vaping and smoking status: Evidence from a UK based cohort","volume":"217","author":"JN Khouja","year":"2020","journal-title":"Drug Alcohol Depend."},{"key":"pmed.1003555.ref005","article-title":"Is e-cigarette use in non-smoking young adults associated with later smoking? 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