Exploring the relationship between air pollution, non-alcoholic fatty liver disease, and liver function indicators: a two-sample Mendelian randomization analysis study

Abstract

Background and aims: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder worldwide, with an increasing incidence in recent years. While previous studies have suggested an association between the air pollutant PM2.5 and NAFLD, there is still considerable debate regarding the existence of a clear causal relationship between air pollution and NAFLD. This study aims to employ Mendelian randomization methods to evaluate the causal relationship between major air pollutants and NAFLD.

Method: We conducted Mendelian randomization analyses on a large-scale publicly available genome-wide association study (GWAS) dataset of European populations to dissect the association between air pollutants, NAFLD, and liver function indicators. We used five different analysis methods, including Inverse-variance weighted (IVW), Weighted median, MR-Egger, Simple mode, and Weighted mode, to analyze the data. We also tested for pleiotropy, heterogeneity, and sensitivity of the results.

Results: This study utilized four common exposures related to air pollution and four outcomes related to NAFLD. The results regarding the association between air pollutants and NAFLD (PM2.5: P=0.808, 95% CI=0.37-3.56; PM10: P=0.238, 95% CI=0.33-1.31; nitrogen dioxide: P=0.629, 95% CI=0.40-4.61; nitrogen oxides: P=0.123, 95% CI=0.13-1.28) indicated no statistically significant correlation between them. However, notably, there was a causal relationship between PM10 and serum albumin (ALB) levels (P=0.019, 95% CI=1.02-1.27).

Conclusion: This MR study found no evidence of a causal relationship between air pollution and NAFLD in European populations. However, a statistically significant association was observed between PM10 and ALB levels, suggesting that the air pollutant PM10 may impact the liver's ability to synthesize proteins.

Keywords: Mendelian randomization study; PM2.5; air pollution; causal relationship; liver function indicators; non-alcoholic fatty liver disease.

Figure 1

Flow chart of this Mendelian randomization study.

Figure 2

Basic assumptions of Mendelian randomization and main design of this study.

Figure 3

Scatter plots for causal single nucleotide polymorphism (SNP) effect of air pollution (particulate matter, nitrogen dioxide, and nitrogen oxides) on NAFLD in the European population. We plot each black point to represent each SNP on the exposure (horizontal axis) and the outcome (vertical axis), with error bars corresponding to each standard error (SE). The slope of each line corresponds to the combined estimate using each method of the inverse variance weighted (light blue line), the MR-Egger (blue line), the simple mode (light green line), the weighted median (green line), and the weighted mode (pink line). (A) PM2.5; (B) PM10; (C) Nitrogen dioxide; (D) Nitrogen oxides.

Figure 4

Leave-one-out analysis plot for causal SNP effect of air pollution (particulate matter, nitrogen dioxide, and nitrogen oxides) on NAFLD in the European population. The error bars indicate the 95% confidence interval (CI). (A) PM2.5; (B) PM10; (C) Nitrogen dioxide; (D) Nitrogen oxides.

Figure 5

Forest plots for causal SNP effect of air pollution (particulate matter, nitrogen dioxide, and nitrogen oxides) on NAFLD in the European population. The error bars indicate the 95% confidence interval (CI). (A) PM2.5; (B) PM10; (C) Nitrogen dioxide; (D) Nitrogen oxides.

Figure 6

Funnel plots for causal SNP effect of air pollution (particulate matter, nitrogen dioxide, and nitrogen oxides) on NAFLD in the European population. (A) PM2.5; (B) PM10; (C) Nitrogen dioxide; (D) Nitrogen oxides.