Abstract
IgA nephropathy (IgAN) is the leading cause of end-stage renal disease, although its mechanisms remain incompletely understood. Previous studies have identified metabolites associated with IgAN, but their causal relationships require further investigation. This study employed a 2-sample Mendelian randomization (MR) approach to assess the causal relationships between 1400 serum metabolites and IgAN. Causal effects between these metabolites and IgAN were estimated using the inverse-variance weighted method. Additional analyses, including MR-Egger regression, weighted median, simple mode, and weighted mode methods, were conducted to refine and validate these findings. Pleiotropy and heterogeneity tests were also performed. The initial analysis identified 9 known and 4 novel metabolites associated with IgAN. Notably, Acisoga was found to increase the risk of IgAN, whereas serine exhibited a protective effect; both findings were confirmed by robust statistical tests (P < .05). This initial MR analysis highlights 2 metabolites significantly linked to IgAN, providing valuable insights into the disease' s underlying mechanisms for clinical research. Further investigation is needed to validate these findings.