Causal Inference of Different Smoke Exposure Statuses and Influenza Risk: Insights From a Mendelian Randomization Study

Abstract

Introduction

Previous observational studies have suggested a potential association between smoking exposure and influenza infection risk. However, the impact of different smoke exposure statuses on susceptibility to influenza infection remains insufficiently explored. This study employs Mendelian randomization analysis to investigate the causal relationship between smoking exposure statuses, including current tobacco use, household smoking exposure, past smoking history, and the risk of influenza infection.

Methods

The summary-level data for this study were obtained from the FinnGen Consortium R11 and Neale Lab, both outcomes and exposures. To ensure robust results, we employed multiplicative random-effects inverse variance weighting, MR-Egger, and weighted median (WM) methods to analyze single-nucleotide polymorphisms (SNPs). We also conducted Cochran's Q test, MR-PRESSO, and the MR-Egger intercept test to assess heterogeneity and horizontal pleiotropy, ensuring accurate and reliable findings.

Results

Our analysis demonstrated that elevated exposure to current tobacco smoking causally increased the risk of influenza infection, with (OR = 2.032, 95% CI 1.672–2.538, p < 0.001) or without pneumonia (OR = 2.081, 95% CI 1.824–2.338, p = 0.015). No reverse causal relationship was found, and no bidirectional effects were observed for past smoking (OR = 1.108, 95% CI 0.543–2.258, p = 0.779) or household exposure (OR = 1.127, 95% CI −0.209–2.462, p = 0.939).

Conclusion

This analysis identified a significant causal association between current tobacco smoking and increased risk of influenza infection. However, no significant association was observed for other smoking exposures (e.g., former or household smoking). These findings emphasized the importance of considering different types of smoking exposure in clinical influenza prevention and treatment strategies.