A comprehensive analysis of the health effects associated with smoking in the largest population using UK Biobank genotypic and phenotypic data.

ABSTRACT

Background: Smoking is a widespread behavior, while the relationship between smoking and various diseases remains a topic of debate. Objective: We conducted analysis to further examine the identified associations and assess potential causal relationships. Methods: We utilized seven single nucleotide polymorphisms (SNPs) known to be linked to smoking extracting genotype data from the UK Biobank, a large-scale biomedical repository encompassing comprehensive health-related and genetic information of European descent. Phenome-wide association study (PheWAS) analysis was conducted to map the association of genetically predicted smoking status with 1,549 phenotypes. The associations identified in the PheWAS were then meticulously examined through two-sample Mendelian randomization (MR) analysis, utilizing data from the UK Biobank (n = 487,365) and the Sequencing Consortium of Alcohol and Nicotine Use (GSCAN) (n = 337,334). This approach allowed us to comprehensively characterize the links between smoking and disease patterns. Results: The PheWAS analysis produced 34 phenotypes that demonstrated significant associations with smoking (P = 0.05/1460). Importantly, sickle cell anemia and type 2 diabetes exhibited the most significant SNPs (both 85.71% significant SNPs). Furthermore, the MR analyses provided compelling evidence supporting causal associations between smoking and the risk of following diseases obstructive chronic bronchitis (IVW Beta = 0.48, 95% confidence interval (CI) 0.36-0.61, P = 1.62×10-13), cancer of the bronchus (IVW Beta = 0.92, 95% CI 0.68-1.17, P = 2.02×10-13), peripheral vascular disease (IVW Beta = 1.09, 95% CI 0.71-1.46, P = 1.63×10-8), emphysema (IVW Beta = 1.63, 95% CI 0.90-2.36, P = 1.29×10-5), pneumococcal pneumonia (IVW Beta = 0.30, 95% CI 0.11-0.49, P = 1.60×10-3), chronic airway obstruction (IVW Beta = 0.83, 95% CI 0.30-1.36, P = 2.00×10-3) and type 2 diabetes (IVW Beta = 0.53, 95% CI 0.16-0.90, P = 5.08×10-3). Conclusion: This study affirms causal relationships between smoking and obstructive chronic bronchitis, cancer of the bronchus, peripheral vascular disease, emphysema, pneumococcal pneumonia, chronic airway obstruction, type 2 diabetes, in the European population. These findings highlight the broad health impacts of smoking and support smoking cessation efforts.