Journal Article

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

Sanderson, Eleanor, Richmond, Rebecca C., Wootton, Robyn E., Munafò, Marcus R., Church, Billy A., Taylor, Amy E., Khouja, Jasmine N.

2024

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Biology and Life Sciences / Cardiovascular disease / Chronic obstructive pulmonary disease / Cigarettes / Coronary artery disease / Electronic cigarettes / Electronic Nicotine Delivery Systems / Genome-wide association studies / Genome-Wide Association Study / Genomes / Health aspects / Heart diseases / Heart rate / Humans / Lung cancer / Lung diseases / Lung Neoplasms - genetics / Medicine and Health Sciences / Mendelian Randomization Analysis / Metabolism / Metabolites / Nicotine / Nicotine - adverse effects / Nicotine - analysis / Physical Sciences / Pulmonary Disease, Chronic Obstructive - genetics / Respiratory function / Smoke / Smoking / Smoking - adverse effects / Smoking - genetics / Social Sciences / Statistical analysis / Tobacco / Tobacco Products / Tobacco smoke / Tobacco Smoke Pollution