Genetically predicted blood metabolites mediate the association between immune cell characteristics and urolithiasis: A Mendelian randomization study and mediation analysis

Abstract

Urolithiasis, a disease characterized by the formation of urinary stones, is influenced by immune system dysregulation and metabolic factors. This study investigated the interplay between specific immune cell characteristics and blood metabolites in urolithiasis based on Mendelian randomization. We further explored the potential mediating effects of genetically predicted blood metabolites based on mediation analysis. We employed a two-sample Mendelian randomization analysis to examine the association between immune cell properties, blood metabolites, and urolithiasis risk. Genetic instruments for immune cell characteristics and blood metabolites were used to assess causal relationships and mediating pathways. Our results indicate that 10 immune cell characteristics had a unidirectional causal association with urolithiasis risk. We also detected 13 blood metabolites associated with urolithiasis. We identified 4 pathways through which genetically predicted blood metabolites partly mediated the association between specific immune cell characteristics and urolithiasis risk. This suggests potential mechanistic links where altered blood metabolites may play a role in developing urolithiasis through immune system modulation. This Mendelian randomization study highlights the complex relationship between immune responses, blood metabolites, and urolithiasis. The findings underscore the importance of considering both immune cell features and metabolic factors in understanding the pathogenesis of urolithiasis, offering insights into novel therapeutic targets and diagnostic strategies for this disorder.

Keywords: Blood metabolites; Immunity; Mediation analysis; Mendelian randomization study; Urolithiasis.

Figure 1

Flowchart of study.

Figure 2

The heatmap depicting the association between immune cell characteristics and urolithiasis. It shows all the results with IVW p-value < 0.01. The outer circle represents the names of immune cell characteristics, while the inner circle uses different colors to indicate the odds ratio of five Mendelian randomization models.

Figure 3

Bidirectional Mendelian randomization of immune cell characteristics and urolithiasis. (A) Causal effects of immune cells characteristics on urolithiasis. (B) Causal effects of urolithiasis on immune cells characteristics. CI, confidence interval; OR, odds ratio; SNP, single nucleotide polymorphism.

Figure 4

The volcano plot illustrating the link between 1400 blood metabolites and urolithiasis risk. The X-axis represents the logarithmic odds ratio (OR) with a base of 2, and the Y-axis represents the IVW logarithmic p-value with a base of 10. p < 0.01 is considered statistically significant.

Figure 5

Causal effects of blood metabolites on urolithiasis. CI, confidence interval; OR, odds ratio; SNP, single nucleotide polymorphism.

Figure 6

Scatter plots of immune cell characteristics on blood metabolites. (A) The negative direction of CD4 Treg %T cell and 4-hydroxychlorothalonil levels. (B) The positive direction of CD24 on transitional B cells and glycolithocholate levels. (C) The negative direction of HLA DR on DC and glycolithocholate levels. (D) The negative direction of HLA DR on B cells and 1-oleoyl-2-linoleoyl-GPE (18:1/18:2) levels.

Figure 7

Estimated proportion of the association between immune cell characteristics and urolithiasis mediated by blood metabolites. (A) CD4 Treg %T cell mediated by 4-hydroxychlorothalonil. (B) CD24 on transitional B cells mediated by glycolithocholate levels. (C) HLA DR on DC mediated by glycolithocholate levels. (D) HLA DR on B cells mediated by 1-oleoyl-2-linoleoyl-GPE (18:1/18:2). IE, indirect effect; DE, direct effect. ∗∗∗p < 0.001.

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