Abstract Sun1008: GATM Identified as a Potential Drug Target for Cardiac Arrest Through Multi-Omics Mendelian Randomization Integrating GWAS, eQTL, and pQTL Data

Abstract

Background: Targeted therapy for cardiac arrest remains a significant clinical challenge. Multi-omics Mendelian randomization (MR) analysis provides a novel framework for identifying potential drug targets. Method: Summary-data-based MR (SMR) and aggregated data-based MR analyses were conducted to investigate therapeutic targets for cardiac arrest by integrating gene expression and protein quantitative trait loci (eQTL and pQTL) data. Colocalization analysis was performed to determine whether phenotypically related traits share common genetic variants within specific genomic regions. Result: SMR analysis identified 187 potential drug targets in blood. After false discovery rate correction (P FDR <0.05), 28 targets were significantly associated with cardiac arrest (10 negatively correlated, 18 positively correlated). Colocalization analysis revealed strong genetic overlap between glycine amide transferase(GATM）and cardiac arrest (PPH4=0.96). pQTL MR analysis showed that elevated plasma GATM levels were associated with an increased risk of cardiac arrest (OR= 2.120, 95%CI 1.514-2.969, P Wald ratio =1.22E-05), consistent with eQTL findings. Among cardiac arrest patients, higher blood mRNA expression of GATM correlated with worse cerebral performance category (CPC) scores. Receiver operating characteristic (ROC) analysis further confirmed that GATM expression predicted poor neurological outcomes. Conclusion: The findings support a causal relationship between elevated GATM expression and increased risk of cardiac arrest. GATM is highlighted as a promising therapeutic target, offering new avenues for targeted intervention strategies.