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To explore the causal relationship between blood metabolites and the risk of coronary artery disease (CAD) using a two-sample Mendelian randomization (MR) approach. Based on the data from a large-scale metabolome-based genome-wide association study (mGWAS) and the GWAS of CAD, we investigated the causality between blood metabolites and CAD using an inverse variance weighted (IVW) method and another 4 two-sample MR models. Heterogeneity, horizontal pleiotropy, and sensitivity tests were performed to evaluate the stability and reliability