Gene-by-Environment Interaction in Non-Alcoholic Fatty Liver Disease and Depression: The Role of Hepatic Transaminases

Abstract

Non-alcoholic fatty liver disease (NAFLD) encompasses a range of liver conditions, from benign fatty accumulation to severe fibrosis. The global prevalence of NAFLD has risen to 25-30%, with variations across ethnic groups. NAFLD may advance to hepatocellular carcinoma, increases cardiovascular risk, is associated with chronic kidney disease, and is an independent metabolic disease risk factor. Assessment methods for liver health include liver biopsy, magnetic resonance imaging, ultrasound, and vibration-controlled transient elastography (VCTE by FibroScan). Hepatic transaminases are cost-effective and minimally invasive liver health assessment methods options. This study focuses on the interaction between genetic factors underlying the traits (hepatic transaminases and the FibroScan results) on the one hand and the environment (depression) on the other. We examined 525 individuals at risk for metabolic disorders. We utilized variance components models and likelihood-based statistical inference to examine potential GxE interactions in markers of NAFLD, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the AST/ALT ratio, and Vibration-Controlled Transient Elastography (VCTE by FibroScan). We calculated the Fibroscan-AST (FAST) score (a score that identifies the risk of progressive non-alcoholic steatohepatitis (NASH) and screened for depression using the Beck Depression Inventory-II (BDI-II). We identified significant G x E interactions for AST/ALT ratio x BDI-II, but not AST, ALT, or the FAST score. Our findings support that genetic factors play a role in hepatic transaminases, especially the AST/ALT ratio, with depression influencing this relationship. These insights contribute to understanding the complex interplay of genetics, environment, and liver health, potentially guiding future personalized interventions.