Genetic Evidence for Causal Relationships Between Circulating Cathepsin Levels and Chronic Obstructive Pulmonary Disease: A Mendelian Randomization Study
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background: Cathepsins, a family of lysosomal proteolytic enzymes, have been implicated in the pathogenesis of various complex diseases, including chronic obstructive pulmonary disease (COPD). However, the causal relationship between cathepsins and COPD remains unclear. Methods: This study employed Mendelian randomization (MR) to investigate the potential causal effects of cathepsin levels on COPD risk. This MR analysis utilized genetic data from individuals of European ancestry in the INTERVAL study and FinnGen consortium. Specifically, summary-level genetic data for 9 cathepsins (B, E, F, G, H, O, L2, S, and Z) were obtained from the INTERVAL study, while COPD summary statistics were sourced from the FinnGen consortium. We conducted comprehensive MR analyses, including univariable MR, reverse MR, multivariable MR (MVMR), and MR least absolute shrinkage and selection operator, to assess causal relationships between cathepsin levels and COPD risk. Results: =0.025, 95% CI = 1.008-1.132), respectively. Furthermore, these 2 cathepsins were independent risk factors for COPD after adjusting for smoking. Conclusions: To our knowledge, this is the first MR study to systematically evaluate the causal role of cathepsins in COPD. Further research, particularly clinical trials, is warranted to validate these associations and explore the therapeutic potential of targeting cathepsins in COPD management.
Authors: Chao Duan, Ao Zhang, Suyan Tian
Institution: First Hospital of Jilin University
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4413014926