Bidirectional Mendelian randomization study shows causal relationship between high- altitude adaptation and liver diseases

Abstract

To investigate the causality between high-altitude adaptation (HAA) and multiple liver diseases, we applied a Mendelian randomization (MR) study. The genome-wide association studies (GWASs) of HAA and eleven phenotypes of liver diseases/traits were used for this study, including autoimmune hepatitis (AIH), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic bile duct cancer (BtC), chronic hepatitis-B (CHB), chronic hepatitis-C (CHC), γ-glutamyl transpeptidase (GTT), acute hepatitis by hepatitis-A virus (HAV), hepatic cancer (HepC) and total bilirubin (TBil). Our study genetically predicted a significant causal impact of HAA on GTT (odds ratio, 1.601; 95% CI, 1.204–2.129; P = 0.0012). An interesting finding emerged that the association between GGT and HAA also reached statistically significant even the causal direction was reversed (odds ratio, 1.01; 95% CI, 1.003–1.011; P = 0.0013). In conclusions, our study indicates a mutually causal association between HAA and GGT. These novel insights may facilitate the design of targeted preventive measures and therapeutic interventions for both liver diseases and the process of adapt to plateau environment.