Year: 2025
Type: article
Study design: Observational Study
Abstract: INTRODUCTIONChronic Obstructive Pulmonary Disease (COPD) is a complex condition influenced by both genetic and environmental factors.This study aims to identify potential biomarkers and explore the associations between specific maker genes, smoking initiation, and COPD.METHODS We used Mendelian randomization (MR) with inverse variance weighting (IVW) to identify significant associations (p<0.05).Genetic instruments for smoking initiation (Genome-Wide Association Study [GWAS]: ieu-b-4877) and Out at First (OAF) (cis-expression Quantitative Trait Locus [eQTL] GWAS) were selected based on single nucleotide polymorphisms (SNPs) with p<5×10 -8 .COPD GWAS data served as the outcome.Two-sample MR analysis estimated causal effects of smoking initiation/OAF on COPD.Mediation analysis explored the role of 731 immune cell phenotypes in these associations. RESULTSWe identified OAF as a key genetic marker associated with COPD risk, with the eQTL analysis yielding an odds ratio (OR) of 1.09 (95% CI: 1.02-1.17,p=0.01).The IVW analysis for smoking initiation-COPD indicated an OR of 1.89 (95% CI: 1.69-2.11,p<0.001).Mediation analysis revealed that the immune cell phenotype CD14-CD16-absolute count (AC) (GCST90001581) accounted for 30.16% and 4.27% of the mediation in the OAF-COPD and smoking initiation-COPD associations, respectively.CONCLUSIONS The MR results suggest that OAF may be a genetic risk factor for COPD, with immune cell phenotypes, particularly CD14-CD16-AC, potentially playing a mediating role in COPD development.Smoking initiation is also positively correlated with COPD, playing an important role in its pathogenesis.
Source: Tobacco Induced Diseases
DOI: 10.18332/tid/210379
Authors: Feng You, Kai Xu, Gengzhong Chen, Siwen Chen, Qiheng Yuan, Bianjin Sun
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,372
OpenAlex ID: W4414995379