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

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Complex exposure; EWAS; Environmentally hazardous chemicals; Liver enzyme.

Fig. 1. Flow of study participants selection.

KoNEHS: Korean National Environmental Health Survey. ^*Due to COVID-19, blood and urine sampling was not properly performed in 2020.

Fig. 2. Manhattan plot of EWAS of environmentally hazardous chemicals for elevated liver enzymes. (A) Manhattan plot of EWAS for elevated aspartate aminotransferase. (B) Manhattan plot of EWAS for elevated alanine aminotransferase. (C) Manhattan plot of EWAS for elevated gamma glutamyl transferase. X-axis shows the groups of categorized chemicals. Y-axis shows −log_10(p-value) of the generalized linear model analysis with each variables with elevated liver enzymes. Each categorized group was represented as same color of dots. The statistically significant cut-off values of false discovery rate < 0.05 were represented as grey dashed line.

MEOHP: 2-ethyl-5-oxohexyl phthalate; PAH: polycyclic aromatic hydrocarbon; PBA: 3-phenoxybenzoic acid; BPS: bisphenol S; PFOS: perfluorooctanesulfonate; PFDeA: perfluorodecanoic acid; EWAS: environment-wide association study; 3m: 3 months; rec.: recent; cont.: container; med.: medicine.