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

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.