Estimating the health impact of nicotine exposure by dissecting the effects of nicotine versus non-nicotine constituents of tobacco smoke: A multivariable Mendelian randomisation study.

Autor: Khouja JN; School of Psychological Science, University of Bristol, Bristol, United Kingdom.; Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom., Sanderson E; Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom., Wootton RE; School of Psychological Science, University of Bristol, Bristol, United Kingdom.; Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.; Nic Waals Institute, Lovisenberg diakonale sykehus, Oslo, Norway., Taylor AE; Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom., Church BA; School of Psychology and Vision Sciences, University of Leicester, United Kingdom., Richmond RC; Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom., Munafò MR; School of Psychological Science, University of Bristol, Bristol, United Kingdom.; Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.; NIHR Bristol Biomedical Research Centre, Bristol, United Kingdom.
Jazyk: angličtina
Zdroj: PLoS genetics [PLoS Genet] 2024 Feb 09; Vol. 20 (2), pp. e1011157. Date of Electronic Publication: 2024 Feb 09 (Print Publication: 2024).
DOI: 10.1371/journal.pgen.1011157
Abstrakt: The detrimental health effects of smoking are well-known, but the impact of regular nicotine use without exposure to the other constituents of tobacco is less clear. Given the increasing daily use of alternative nicotine delivery systems, such as e-cigarettes, it is increasingly important to understand and separate the effects of nicotine use from the impact of tobacco smoke exposure. Using a multivariable Mendelian randomisation framework, we explored the direct effects of nicotine compared with the non-nicotine constituents of tobacco smoke on health outcomes (lung cancer, chronic obstructive pulmonary disease [COPD], forced expiratory volume in one second [FEV-1], forced vital capacity [FVC], coronary heart disease [CHD], and heart rate [HR]). We used Genome-Wide Association Study (GWAS) summary statistics from Buchwald and colleagues, the GWAS and Sequencing Consortium of Alcohol and Nicotine, the International Lung Cancer Consortium, and UK Biobank. Increased nicotine metabolism increased the risk of COPD, lung cancer, and lung function in the univariable analysis. However, when accounting for smoking heaviness in the multivariable analysis, we found that increased nicotine metabolite ratio (indicative of decreased nicotine exposure per cigarette smoked) decreases heart rate (b = -0.30, 95% CI -0.50 to -0.10) and lung function (b = -33.33, 95% CI -41.76 to -24.90). There was no clear evidence of an effect on the remaining outcomes. The results suggest that these smoking-related outcomes are not due to nicotine exposure but are caused by the other components of tobacco smoke; however, there are multiple potential sources of bias, and the results should be triangulated using evidence from a range of methodologies.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Khouja et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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