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. 2025 Apr 12;25(1):116.
doi: 10.1007/s10238-025-01644-9.

PM2.5 increases the risk of early-onset COPD mediated by smoking and shared genes: a large-scale genetic analysis

Jie Wen #  1   2 , Yanlin Yang #  3 , Hao Zhang  3 , Wantao Wu  4 , Ziyu Dai  1   2 , Xisong Liang  1   2 , Shuyuan Chen  5
Affiliations

PM2.5 increases the risk of early-onset COPD mediated by smoking and shared genes: a large-scale genetic analysis

Jie Wen et al. Clin Exp Med. .

Abstract

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mortality worldwide. However, whether air pollutants can cause COPD remains unknown. Summary data for the genome-wide association study of each phenotype were obtained from the publicly available datasets. Using single-nucleotide polymorphisms as instrumental variables, we performed Mendelian randomization (MR) to assess the relationship among PM2.5, smoking and early-onset COPD. A large-scale genetic analysis is performed to investigate the biological pathways. In MR, exposure to higher PM2.5 increased the risk of early-onset COPD (IVW, OR (95% CI) = 1.63 (1.15, 2.31), p = 5.60E-03) but had no association with later-onset COPD. In addition, cigarettes per day (IVW, OR (95% CI) = 1.71 (1.46, 1.99), p = 1.60E-11) was positively associated with the risk of early-onset COPD, while age of smoking initiation (IVW, OR (95% CI) = 0.39 (0.27, 0.57), p = 1.21E-06) had a negative effect. In addition, two smoking behaviors could be mediators between PM2.5 and early-onset COPD (p < 0.05). Furthermore, 136 significantly enriched biological pathways of PM2.5 potentially causing early-onset COPD were identified in a large-scale genetic analysis. This study provides strong evidence that exposure to higher PM2.5 was causally associated with smoking behavior and early-onset COPD. Smoking behavior acted as a mediator between PM2.5 and early-onset COPD. More attention should be given to people exposed to higher PM2.5 for the prevention of smoking and COPD.

Keywords: COPD; Environment; Genetic analysis; Mendelian randomization; PM2.5; Pollutants; Smoking.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable.

Figures

Fig. 1
Fig. 1
Study design. A Pattern diagrams for TSMR and MVMR. B Pattern diagrams for mediation analysis. C Flowchart of potential mechanism investigation. The figure was created by Biorender.com
Fig. 2
Fig. 2
Schematic diagram of the outcomes of mediation analysis. CigPerDay, cigarettes per day; AgeSmokInt, age of smoking initiation; SNP, single-nucleotide polymorphism; OR, odds ratio; P, P value
Fig. 3
Fig. 3
Multivariate Mendelian randomization. CigPerDay and AgeSmokInt were adjusted separately to verify the direct causal effect of PM2.5 on early-onset COPD. CigPerDay, cigarettes per day; AgeSmokInt, age of smoking initiation; SNP, single-nucleotide polymorphism; OR, odds ratio; P, P value
Fig. 4
Fig. 4
Enrichment analysis of biological pathways
See this image and copyright information in PMC

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