Discovery of urinary metabolite biomarkers of psychiatric disorders using two-sample Mendelian randomization

Abstract Background Mental health disorders cause substantial patient suffering, which could be alleviated through early diagnostic biomarkers. While biomarker discovery is costly, genetic methods utilizing data from large-scale studies, such as Mendelian randomization, may provide a cost-effective approach. Methods A two-sample Mendelian randomization analysis was conducted to identify potential urinary biomarkers of seven psychiatric disorders using summary statistics from GWAS data. Results The analysis revealed 67 analyte-disorder associations, of which 21 were exclusive to a single disorder. Notable associations were observed between tyrosine and schizophrenia (β = -0.041, SE = 0.013, Q = 0.027), creatine and bipolar disorder (β = -0.077, SE = 0.019, Q = 0.002), pyridoxal (β = 0.10, SE = 0.03, Q = 0.042) and ferulic acid 4-sulfate (β = 0.077, SE = 0.025, Q = 0.037) to anorexia nervosa, and N, N-dimethylglycine to ADHD (β = -0.39, SE = 0.11, Q = 0.008). Conclusion The results identify candidate urinary biomarkers and demonstrate the utility of genetic instruments for biomarker discovery, warranting experimental validation in independent cohorts. Clinical trial number Not applicable.