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This study investigates the relationship between obesity and the hepatic ASB3–CPT1A pathway, proposing a hypothesis on tissue-specific causal effects. Utilizing bidirectional Mendelian randomization methods, including GTEx eQTLs and GWAS datasets, the research examines both forward and reverse designs alongside sensitivity tests. Results indicate that hepatic ASB3 is associated with increased BMI (β=0.026, P=0.011), while no significant effects on MASLD or lipid levels were found after FDR...