Research Paper Volume 16, Issue 10 pp 8922—8943
Potential marker genes for chronic obstructive pulmonary disease revealed based on single-cell sequencing and Mendelian randomization analysis
- 1 General Hospital of Northern Theater Command, Shenyang 110000, Liaoning, China
- 2 East China Normal University Wuhu Affiliated Hospital (The Second People’s Hospital of Wuhu City), Wuhu 241000, Anhui, China
- 3 The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei 230022, Anhui China
Received: December 5, 2023 Accepted: April 15, 2024 Published: May 23, 2024
https://doi.org/10.18632/aging.205849How to Cite
Copyright: © 2024 Sun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Progress is being made in the prevention and treatment of chronic obstructive pulmonary disease (COPD), but it is still unsatisfactory. With the development of genetic technology, validated genetic information can better explain COPD.
Objective: The study utilized scRNA-seq and Mendelian randomization analysis of eQTLs to identify crucial genes and potential mechanistic pathways underlying COPD pathogenesis.
Mehods: Single-cell sequencing data were used to identify marker genes for immune cells in the COPD process. Data on eQTLs for immune cell marker genes were obtained from the eQTLGen consortium. To estimate the causal effect of marker genes on COPD, we selected an independent cohort (ukb-b-16751) derived from the UK Biobank database for two-sample Mendelian randomization analysis. Subsequently, we performed immune infiltration analysis, gene set enrichment analysis (GSEA), and co-expression network analysis on the key genes.
Results: The 154 immune cell-associated marker genes identified were mainly involved in pathways such as vacuolar cleavage, positive regulation of immune response and regulation of cell activation. Mendelian randomization analysis screened four pairs of marker genes (GZMH, COTL1, CSTA and CD14) were causally associated with COPD. These four key genes were significantly associated with immune cells. In addition, we have identified potential transcription factors associated with these key genes using the Cistrome database, thus contributing to a deeper understanding of the regulatory network of these gene expressions.
Conclusions: This eQTLs Mendelian randomization study identified four key genes (GZMH, COTL1, CSTA, and CD14) causally associated with COPD, providing new insights for prevention and treatment of COPD.