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

## TL;DR

This study finds that three inflammatory factors in the blood are causally linked to tic disorders, with two increasing risk and one reducing it.

## Contribution

Identifies causal relationships between IL-17, MIF, and PDGF-BB with tic disorders using Mendelian randomization.

## Key findings

- IL-17 and MIF increase the risk of tic disorders.
- PDGF-BB is protective against tic disorders.
- Results are robust with no heterogeneity or pleiotropy detected.

## Abstract

•IL-17, MIF, and PDGF-BB are causally linked to tic disorders.•IL-17 and MIF increase TD risk, while PDGF-BB is protective.•Study results are robust with strong statistical power.

IL-17, MIF, and PDGF-BB are causally linked to tic disorders.

IL-17 and MIF increase TD risk, while PDGF-BB is protective.

Study results are robust with strong statistical power.

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

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.

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.

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.