Cross ethnic Mendelian randomization analysis reveals causal relationship between air pollution and risk of kidney stones

Abstract

Accumulating evidence has indicated that exposures to air pollution increase the odds of kidney stones. However, the previous research methods were limited. To address this gap, we employed genome-wide association studies (GWAS) datasets and Mendelian randomization (MR) to verify the causation. Applying publicly accessible summary datasets from UK Biobank, FinnGen consortium and Biobank Japan, a two-sample MR, and further multivariate MR were carried out to calculate the causality between air pollution [particulate matter 2.5 (PM2.5), PM2.5 absorbance, PM2.5-10, PM10, nitrogen dioxide, and nitrogen oxides] and kidney stone risk in three different populations (European, East Asian, and South Asian). The inverse variance weighted (IVW) was utilized for its first-step assessment, supplemented with MR-Egger, weighted median, Cochran's Q test, MR-Egger intercept and leave-one-out analysis to ensure the robustness. Employing IVW, we discovered in the European population that PM2.5 absorbance was statistically correlated with kidney stone risk (odds ratio (OR) = 1.40; 95% confidence interval (CI), 1.01-1.94; P = 0.04), with no heterogeneity, pleiotropy, or sensitivity observed. Additionally, the MVMR result revealed the directly causative connection between a single PM2.5 absorbance and the increase in kidney stone risk (OR = 1.77, 95%CI: 1.06-2.98, p = 0.03). Our investigation proposed the correlation between PM2.5 absorbance and an increased risk of kidney stones in European populations. The control of air pollution, especially PM2.5, may have crucial implications for the prevention of kidney stones.

Keywords: Air pollution; Genome-wide association studies; Kidney stone disease (kidney stone); Mendelian randomization; PM2.5 absorbance.

Fig. 1

The overview flowchart of hypothesis and schematic design of our MR study. PM, Particulate matter; IV, Instrumental variable; SNPs, Single-nucleotide polymorphisms; MR, Mendelian randomization; LD, link imbalance.

Fig. 2

MR results of causal relationship between exposure to PM2.5 absorbance and kidney stone outcome in three different populations. PM, Particulate matter; GWAS, Genome-Wide association study; N of SNPs, number of single-nucleotide polymorphisms; CI, confidence interval.

Fig. 3

Scatter plot (a), funnel plot (b), and leave-one-out analysis (c) for causal SNP effect of PM2.5 absorbance on kidney stone in European population.