Relationship between Tic disorders and 41 inflammatory factors in circulating blood: a two-sample Mendelian randomization study

Abstract

Objective  To investigate the causal associations between 41 circulating inflammatory factors and Tic Disorders (TD) via the Mendelian Randomization (MR) approach.

Methods  Single-Nucleotide Polymorphisms (SNPs) related to 41 circulating inflammatory factors were obtained from published Genome-Wide Association Studies (GWASs). The outcome event, TD, was sourced from the FinnGen Biobank database. MR was employed to explore the causal relationship between these inflammatory factors and TD. Causal inference was performed via Inverse Variance Weighted (IVW), MR-Egger, and Weighted Median (WM) methods. Heterogeneity was assessed by Cochran's Q statistic and the leave-one-out method. Horizontal pleiotropy was examined with MR-Egger regression and MR-PRESSO. SNPs with horizontal pleiotropy were removed via the PhenoScanner database to ensure result reliability.

Results  MR analysis revealed significant causal associations between three circulating inflammatory factors and TD. Increased levels of Interleukin-17 (IL-17) and macrophage Migration Inhibitory Factor (MIF) were associated with an increased risk of TD (OR = 2.329, 95 % CI [1.069-5.078], p = 0.033; OR = 2.267, 95 % CI [1.097-4.686], p = 0.027), whereas increased levels of Platelet-Derived Growth Factor BB (PDGF-BB) were linked to a reduced incidence of TD (OR = 0.750, 95 % CI [0.387-1.453], p = 0.023). No causal relationships were found for other inflammatory factors. No heterogeneity or horizontal pleiotropy was detected during the study, and the MR statistical power (power > 80 %) confirmed the reliability of these three findings.

Conclusion  MR analysis revealed causal links between IL-17, MIF, PDGF-BB and TD, suggesting important clinical implications for the development of targeted prevention and treatment strategies for TD.