Multi-omics integration identifies core genes, molecular subtypes, and IDI1-centered immune microenvironment mechanisms in coronary artery disease
Qitian Sun1, Zeyu Zhou2, Shuwei Liang2
1Affiliated Hospital of Chengde Medical College, Department of Endocrinology, Chengde, China.
Background:
Coronary artery disease (CAD) is the leading cause of death worldwide, but its molecular mechanisms remain unclear.
Methods:
We integrated transcriptomic datasets (GSE113079, GSE98583, GSE71226) and single-cell RNA sequencing data (GSE159677) from GEO. Differential expression analysis, WGCNA, machine learning, molecular clustering, immune infiltration analysis, CellChat, in silico knockout, and PheWAS were applied to investigate CAD-related molecular networks.
Results:
We identified 99 DEGs and the MEturquoise module as a CAD-associated module. Machine learning initially identified four candidate genes (RC3H1, IDI1, RAB2A, and SIRPB2); however, only IDI1 was retained after external validation and single-cell intersection. Single-cell analysis revealed macrophage expansion and specific IDI1 enrichment in Cycling cells and immune populations. CAD was classified into two molecular subtypes with distinct immune profiles. Cell communication analysis identified SPP1, TNF, CCL, and MIF pathways as key inflammatory regulators. Virtual knockout simulation of IDI1 affected hemostasis, Toll-like receptor signaling, and collagen degradation pathways. PheWAS showed no significant phenotype-wide associations for IDI1.
Conclusion:
This study identified IDI1 as a CAD-associated candidate gene, revealed immune-based molecular subtypes of CAD, and suggested that IDI1 and inflammatory signaling pathways may serve as potential therapeutic targets, providing insights into precision classification and targeted therapy for CAD.
