Environment-wide association study of elevated liver enzymes: results from the Korean National Environmental Health Survey 2018-2022.

Abstract

Environmental exposure is characterized by low concentration, chronic, and complex exposure. Traditional epidemiological studies show limitations in reflecting these characteristics since they usually focus on a single or very limited number of exposure factors at a time. In this study, we adopted the methodology of environment-wide association study (EWAS) to figure out the association of human liver function with various environmentally hazardous substances. We analyzed 2,961 participants from the Korean National Environmental Health Survey Cycle 4 (2018-2020). Using generalized linear model (GLM) analysis, we analyzed the association of 72 variables with 3 liver function indices (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and gamma glutamyl transferase [GGT]). Finally, we visualized our results with Manhattan plot. In GLM analysis, perfluorooctanesulfonate were positively associated with ALT (odds ratio [OR]: 2.2; 95% confidence interval [CI]: 1.39-3.46; p adjusted = 0.0147) and perfluorodecanoic acid showed positive association with GGT (OR: 2.73; 95% CI: 1.36-5.5; p adjusted = 0.0256). Plasma mercury showed positive association with GGT (OR: 1.45; 95% CI: 1.14-1.84; p adjusted = 0.0315). Using a plastic container while keeping food in the refrigerator was associated with elevated GGT compared to using a glass container (OR: 1.51; 95% CI: 1.16-1.95; p adjusted = 0.0153). 2-ethyl-5-oxohexyl phthalate, showed a negative trend with all 3 indices, with AST (OR: 0.54; 95% CI: 0.39-0.73; p adjusted = 0.00357), ALT (OR: 0.5; 95% CI: 0.34-0.75; p adjusted = 0.036), GGT (OR: 0.55; 95% CI: 0.4-0.76; p adjusted = 0.00697). Bisphenol S and frequent use of sunblock cream showed negative association with ALT (OR: 0.77; 95% CI: 0.66-0.89), and GGT (OR: 0.25; 95% CI: 0.11-0.55), respectively. We conducted an exploratory study on environmental exposure and human liver function. By using EWAS methodology, we identified 7 factors that could have potential association with liver function.