Journal of Shandong University (Health Sciences) ›› 2026, Vol. 64 ›› Issue (6): 104-114.doi: 10.6040/j.issn.1671-7554.0.2025.1159

• Public Health and Preventive Medicine • Previous Articles    

Integrative cross-omics analysis identifies pleiotropic genes shared by coronary artery disease and chronic obstructive pulmonary disease

CHEN Xinyi1,2, HUANG Xin3,4, SUN Xiubin1,2, WANG Shukang1,2, YUAN Zhongshang1,2   

  1. 1. Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China;
    2. National Institute for Health and Medical Big Data, Jinan 250003, Shandong, China;
    3. Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China;
    4. Institute of Brain Science and Brain-inspired Research, Shandong First Medical University (Shandong Academy of Medical Sciences), Jinan 250021, Shandong, China
  • Published:2026-06-29

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Abstract: Objective To integrate transcriptome-wide association studies(TWAS)with pleiotropy analysis under a composite null hypothesis and to explore potential pleiotropic genes for coronary artery disease(CAD)and chronic obstructive pulmonary disease(COPD)from a transcriptomic perspective, providing new insights into the comorbid mechanisms of CAD and COPD. Methods Genome-wide association study(GWAS)summary data for CAD and COPD were obtained from the Million Veteran Program of The Department of Veterans Affairs, and gene expression reference weights for whole blood were derived from GTEx V8. TWAS was conducted using FUSION, and potential pleiotropic genes for CAD and COPD were analyzed using the gPLACO method developed in this study. Furthermore, enrichment analysis, protein-protein interaction analysis, Mendelian randomization analysis, and differential gene expression analysis were conducted on the CAD-COPD pleiotropic genes. Results After Benjamini-Hochberg correction, FUSION identified a total of 794 genes associated with CAD and 463 genes associated with COPD. gPLACO identified 79 pleiotropic genes shared between CAD and COPD, of which 62 were simultaneously significant in TWAS results for both diseases. GO enrichment analysis and transcription factor target gene enrichment further revealed potential biological pathways underlying CAD-COPD comorbidity, including carnitinetransmembrane transporter activity(P=6.03×10-7)and MEF2C target gene(P=5.01×10-3). Further protein-protein interaction analysis, Mendelian randomization analysis, and differential gene expression analysis also suggested STARD3 as a potential pleiotropic gene for CAD-COPD. Conclusion STARD3 is a potential pleiotropic gene for CAD-COPD, underscoring the critical roles of carnitine metabolism and endothelial function in their shared pathophysiology.

Key words: Coronary artery disease, Chronic obstructive pulmonary disease, Pleiotropic genes, Multi-omics data integration, Transcriptome-wide association study

CLC Number: 

  • R541.4
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