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

Ciai Lai; Guolin Huang; Xi Chen; Xionghan Lian; Xin Li; Wei He; Guangliang Luo; Aiyuan Cai

doi:10.1016/j.clinsp.2025.100649

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

Clinics (Sao Paulo). 2025 Jul 10:80:100649. doi: 10.1016/j.clinsp.2025.100649. Online ahead of print.

Authors

Ciai Lai¹, Guolin Huang², Xi Chen², Xionghan Lian³, Xin Li¹, Wei He¹, Guangliang Luo¹, Aiyuan Cai⁴

Affiliations

¹ Shenzhen Hospital, Guangzhou University of Chinese Medicine, Shenzhen, PR China.
² Guangzhou University of Chinese Medicine, Guangzhou, PR China.
³ Fujian University of Traditional Chinese Medicine, Fuzhou, PR China.
⁴ Shenzhen Hospital, Guangzhou University of Chinese Medicine, Shenzhen, PR China. Electronic address: cai18718234370@163.com.

PMID: 40644836
DOI: 10.1016/j.clinsp.2025.100649

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.

Keywords: IL-17; Inflammatory factors; MIF; Mendelian randomization; PDGF-BB; Tic disorders.