Early detection of Parkinson's disease through multiplex blood and urine biomarkers prior to clinical diagnosis.

Blood and urine biomarkers are commonly used to diagnose and monitor chronic diseases. We initially screened 67 biomarkers, including 4 urine biomarkers and 63 blood biomarkers, and identified 13 blood biomarkers significantly associated with Parkinson's disease (PD). Among these, we discovered three novel markers demonstrating strong associations: phosphate (P = 1.81 × 10^-3), AST/ALT ratio (P = 8.53 × 10^-6), and immature reticulocyte fraction (IRF) (P = 3.49 × 10^-20). We also substantiated eight well-studied biomarkers and elucidated the roles of two previously ambiguous biomarkers. Our analyses confirmed IGF-1 (P = 7.46 × 10^-29) as a risk factor, and C-reactive protein (CRP) (P = 1.43 × 10^-3) as protective against PD. Genetic analysis highlighted that IRF, CRP, and IGF-1 share significant genetic loci with PD, notably at MAPT, SETD1A, HLA-DRB1, and HLA-DQA1. Furthermore, Mendelian randomization (MR) analysis suggested potential causal associations between IGF-1, CRP, and PD. We identified several blood biomarkers that may be associated with the risk of developing PD, providing valuable insights for further exploration of PD-related biomarkers.