Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Apr 30;25(1):209.
doi: 10.1186/s12890-025-03658-1.

Smoking and asthma mediate the protective effect of educational attainment on chronic obstructive pulmonary disease risk: a mediation Mendelian randomization analysis

Xue Bai  1 , Lantao Chen  1 , Fenghai Ren  1 , Ying Zhao  1 , Yue Zheng  1 , Yanbo Wang  1 , Sainan Pang  1 , Jian Zhang  1 , Erliang Guo  1 , Huiyan Li  2
Affiliations

Smoking and asthma mediate the protective effect of educational attainment on chronic obstructive pulmonary disease risk: a mediation Mendelian randomization analysis

Xue Bai et al. BMC Pulm Med. .

Abstract

Background: Clinical observational studies have shown an association between educational attainment and a lower incidence of Chronic Obstructive Pulmonary Disease (COPD). However, strong evidence for a causal relationship remains lacking.

Methods: Genome-wide association data for years of schooling, cognitive performance, intelligence, COPD, and COPD-related risk factors such as smoking and asthma were obtained from public databases. We conducted two-sample Mendelian randomization (MR) analyses to assess the causal relationships between years of schooling, cognitive performance, intelligence, and the risk of developing COPD. Sensitivity analyses using MR-Egger and MR-PRESSO were performed to detect and correct for pleiotropy. Multivariable Mendelian randomization analysis was used to identify potential mediators.

Results: Longer years of schooling (OR = 0.537, 95% CI: 0.474-0.608, P = 9.63E-23), higher cognitive performance (OR = 0.793, 95% CI: 0.702-0.895, P = 1.78E-04), and intelligence (OR = 0.813, 95% CI: 0.720-0.919, P = 8.81E-04) were causally associated with a reduced risk of COPD. Longer years of schooling were identified as an independent protective factor for COPD risk (OR = 0.600, 95% CI: 0.472 - 0.762, P = 2.85E-05). Smoking initiation and asthma were identified as mediating factors in the causal relationship between years of schooling and COPD risk. In the reduction of the COPD risk by years of schooling, the mediating effects of smoking initiation and asthma accounted for 32.8% and 6.9% respectively.

Conclusion: These findings provide support for the causal impact of educational attainment on the occurrence of COPD, with a significant portion of this causal effect being mediated through modifiable risk factors. On the premise of controlling socioeconomic - status - related confounders, an increase in educational attainment may provide multi-level intervention targets for COPD prevention through intervenable pathways such as improving health behaviors and environmental exposure.

Keywords: Asthma; Chronic obstructive pulmonary disease; Educational attainment; Mendelian randomization; Smoking.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: The data used in this study is publicly available, therefore further ethical approval is not required. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart of this study. A. Schematic diagram of the principle of Mendelian randomization analysis. B. Establishment of candidate mediating factors between educational attainment and COPD using a two-step Mendelian randomization analysis C. Schematic diagram of the principle of mediation Mendelian randomization analysis
Fig. 2
Fig. 2
Univariable MR results showing the causal effects of Years of schooling, Cognitive performance, and Intelligence on COPD
Fig. 3
Fig. 3
Multivariable MR results showing the causal effects of Years of schooling, Cognitive performance, and Intelligence on COPD after mutual adjustment
Fig. 4
Fig. 4
Multivariable MR results showing the causal effects of Years of schooling, Asthma, and Smoking initiation on COPD after mutual adjustment
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Z L, Z Q. Knowledge, attitude, and practice toward disease prevention among a high-risk population for chronic obstructive pulmonary disease: A cross-sectional study. Int J Nurs Sci. 2023;10(2):238–44. 10.1016/j.ijnss.2023.03.012. - PMC - PubMed
    1. Ruvuna L, Sood A. Epidemiology of chronic obstructive pulmonary disease. Clin Chest Med. 2020;41 3:315–27. - PubMed
    1. Pan Z, Yu H, Liao JL. Probing cellular and molecular mechanisms of cigarette Smoke-Induced immune response in the progression of chronic obstructive pulmonary disease using multiscale network modeling. PLoS ONE. 2016;11(9):e0163192. 10.1371/journal.pone.0163192. - PMC - PubMed
    1. O’Reilly S. Chronic obstructive pulmonary disease. Am J Lifestyle Med Jul-Aug. 2017;11(4):296–302. 10.1177/1559827616656593. - PMC - PubMed
    1. C YW. Independent associations of education, intelligence, and cognition with hypertension and the mediating effects of cardiometabolic risk factors: A Mendelian randomization study. Hypertens (Dallas Tex: 1979). 2023;80(1):192–203. 10.1161/hypertensionaha.122.20286. - PMC - PubMed