• Rutao Bian, Dongyu Li, Xuegong Xu, and Li Zhang.
• Department of Cardiology, Zhengzhou Hospital of Traditional Chinese Medicine, Zhengzhou, Henan 450000, China.
• Postgrad Med J. 2024 Aug 24.

BackgroundImmune inflammation is intricately associated with coronary artery disease (CAD) progression, necessitating the pursuit of more efficacious therapeutic strategies. This study aimed to uncover potential therapeutic targets for CAD and myocardial infarction (MI) by elucidating the causal connection between regulatory immune-related genes (RIRGs) and these disorders.MethodologyWe performed summary data-based Mendelian randomization analysis to assess the therapeutic targets linked to expression quantitative trait loci and methylation quantitative trait loci of RIRGs in relation to CAD and MI. Independent validation cohorts and datasets from coronary artery and left ventricular heart tissue were analyzed. To strengthen causal inference, colocalization analysis and PhenoScanner phenotype scans were employed.ResultsUtilizing multiomics integration, we pinpointed EIF2B2, FCHO1, and DDT as CAD risk genes. Notably, EIF2B2 and FCHO1 displayed significant associations with MI. High EIF2B2 expression, regulated by cg16144293, heightened CAD and MI risk at rs175438. In contrast, enhanced FCHO1 expression, modulated by cg18329931, reduced CAD and MI risk at rs13382133. DDT upregulation influenced by cg11060661 and cg09664220 was associated with decreased CAD risk at rs5760120. Colocalization analysis firmly established these relationships.ConclusionEIF2B2, FCHO1, and DDT represent risk loci for CAD progression within RIRGs. Our identification of these genes enhances understanding of CAD pathogenesis and directs future drug development efforts.© The Author(s) 2024. Published by Oxford University Press on behalf of Fellowship of Postgraduate Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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