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Causal association between cathepsins and asthma: a Mendelian randomization study.
Feng Qiu1,2, Wei Shao1,2, Xue Qin1
1Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu, China.
Scientific Reports
|July 4, 2025
Summary
Elevated levels of cathepsin L2 are linked to increased asthma risk, suggesting this enzyme could be a therapeutic target for the chronic respiratory disease. This study used Mendelian randomization to explore the causal link.
Area of Science:
- Genetics and Respiratory Medicine
- Biochemistry and Molecular Biology
Background:
- Asthma is a prevalent chronic respiratory disease with significant public health implications.
- Cathepsins, a family of proteolytic enzymes, are increasingly recognized for their potential role in asthma pathophysiology.
- The precise causal contribution of cathepsins to asthma development remains to be fully elucidated.
Purpose of the Study:
- To investigate the potential causal relationship between cathepsin levels and asthma.
- To determine if cathepsin L2 is independently associated with asthma risk using genetic data.
- To identify cathepsin L2 as a potential therapeutic target for asthma.
Main Methods:
- Utilized univariate and multivariate Mendelian randomization (MR) analyses.
- Employed genetic data from the INTERVAL study and FinnGen consortium.
- Applied inverse variance weighting (IVW), median weighting, and MR-Egger regression with sensitivity analyses.
Main Results:
- A significant association was found between higher cathepsin L2 levels and increased asthma risk (OR 1.058, P=0.006).
- No evidence of reverse causality was observed, as asthma status did not significantly affect cathepsin L2 levels.
- Multivariable MR and sensitivity analyses confirmed the independent association and ruled out significant pleiotropy.
Conclusions:
- This is the first study to use Mendelian randomization to establish a potential causal link between cathepsins and asthma.
- Cathepsin L2 emerges as a significant factor in asthma pathophysiology.
- Cathepsin L2 represents a promising novel therapeutic target for asthma management.
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