Aminotransferases as causal factors for metabolic syndrome: A bidirectional Mendelian randomization study

Circulating aminotransferases (ALT and AST) have been used as biomarkers for liver injury. The causal relationships between aminotransferases and metabolic syndrome remain ambiguous.

We conducted bidirectional and multivariable Mendelian randomization (MR) analyses between aminotransferases and traits related to metabolic syndrome using genetic variants obtained from genome-wide association studies (GWASs). MR-PRESSO tests were adopted to remove outliers and eliminate pleiotropy. MR steiger tests were conducted to ensure the correct direction of the causal effects.

Both aminotransferases were risk factors for essential hypertension. ALT is a risk factor for type 2 diabetes. The bidirectional causal relationship between ALT and hyperglycemia, serum lipids, and obesity was demonstrated. The effect of fasting glucose on AST was demonstrated, while type 2 diabetes did not affect AST. The effect of HDL-C on ALT and the effect of triglycerides on AST were found in multivariable MR analyses.

Our bidirectional MR analyses suggest that ALT and AST are causally associated with several metabolic syndrome-related traits, especially hypertension and type 2 diabetes. These findings highlight the potential role of aminotransferases as biomarkers and therapeutic targets for metabolic syndrome.