Causal relationship between serum metabolites and risk of psoriatic arthritis: A 2-way Mendelian randomization study

This study aims to investigate the causal effect of serum metabolites on the risk of psoriatic arthritis (PsA). The publicly available data of PsA from the FinnGen BioDatabase were selected to assess the causal relationship between 1400 serum metabolites and PsA by 2-sample 2-way Mendelian randomization (MR) analysis. Inverse variance weighting (IVW) was applied as the main assessment method for causal effects, and sensitivity analyses were performed using the Cochran Q test, MR-Egger regression, MR Pleiotropy RESidual Sum and Outlier, and leave-one-out methods, as well as inverse MR analyses and metabolic pathway enrichment analyses. A potential causal association between 48 serum metabolites and PsA risk was initially identified, involving 27 known metabolites. Among them, gamma-tocopherol/beta-tocopherol (PIVW = .003, odds ratio = 1.297, 95% confidence interval = 1.090-1.545, PFDR = .043) was the risky metabolite with the strongest effect, and dodecanedioate (PIVW < .001, odds ratio = 0.751, 95% confidence interval = 0.659-0.857, PFDR = .001) was the protective metabolite with the strongest effect. The results of each sensitivity analysis were robust. Metabolic pathway enrichment analysis identified 2 important metabolic pathways. A causal relationship between serum metabolites and PsA was revealed, with 14 metabolites, including N-formylaminobenzoic acid, associated with an increased risk of PsA, and 13 metabolites, including arginine, potentially protective against PsA.