Mendelian randomization study of urolithiasis: exploration of risk factors using human blood metabolites

Abstract

Abstract Urolithiasis is a highly prevalent global disease closely related to metabolic factors, but we have little understanding of its underlying mechanisms. Analysis of blood metabolites may enable better comprehension of the underlying biological pathogenesis. The emergence of genome-wide association studies (GWAS) can provide an opportunity to reveal the relationship between urolithiasis and human blood metabolites through Mendelian randomization (MR). In our study, we used a two-sample MR analysis to investigate the causal relationships between urolithiasis and metabolites. The random-effects inverse-variance weighted (IVW) estimation method was used as the major method with several other estimators as supplementary methods. According to our results, we identified 11 known (5 protective and 6 risk) serum metabolites associated with urolithiasis. Among the known protective metabolites, two were lipids (3-hydroxybutyrate (BHBA) and dehydroisoandrosterone sulfate), one amino acid (Isobutyrylcarnitine), one carbohydrate (mannose), and one cofactors and vitamins (Bilirubin (Z, Z)). The known risk metabolites included two lipids (glycerol and cortisone), one amino acid (cysteine), one carbohydrate (erythronate), one peptide (pro-hydroxy-pro) and one fatty acid (eicosenoate (20:1n9 or 11)). Additionally, six metabolic pathways have been identified to be associated with urolithiasis. The evidence of human blood metabolites influencing urolithiasis provided by our results supports future efforts to improve based metabolites therapies to prevent onset of urolithiasis.