Mendelian randomization study on the relationship between inflammatory circulation factors and the risk of tic disorder

doi:10.11852/zgetbjzz2024-1112

Abstract

Abstract: Objective To explore the potential causal relationship between inflammatory factors and Tourette′s disorder (TD), and to investigate the mechanisms for treating TD based on these findings. Methods This Mendelian randomization (MR) study utilized genome-wide association study (GWAS) data on inflammatory factors and TD. Independent genetic loci significantly associated with 91 inflammatory factors were selected as instrumental variables based on predefined thresholds. The inverse-variance weighted (IVW) method was primarily used for MR analysis, with results evaluated using odds ratios (ORs) and 95% confidence intervals (CIs). Sensitivity analysis, including leave-one-out analysis, heterogeneity testing, and horizontal pleiotropy testing, were conducted to validate the stability and reliability of the results. Results The analysis revealed statistically significant associations for CCL25 (OR＝1.331, 95%CI: 1.014-1.747, P＝0.040), CD40 (OR＝1.677, 95%CI: 1.025-2.744, P=0.040), and IL-17C (OR＝0.480, 95%CI: 0.269-0.858, P＝0.013). Conclusion CCL25 and CD40 are associated with an increased risk of TD, while IL-17C is associated with a reduced risk of TD.

Key words: tic disorder, inflammatory factors, Mendel randomization, causality

摘要： 目的探索炎性因子与抽动障碍(TD)之间潜在的因果关系,并以此为靶点探究治疗TD的机制。方法本次孟德尔随机化(MR)研究使用了炎性因子和TD的全基因组关联研究,根据预设的阈值提取与91种炎性因子显著相关的独立遗传位点作为工具变量。主要采用逆方差加权法进行MR分析,根据效应指标优势比(OR)和95%置信区间(95%CI)评估结果。使用留一法、异质性检验、水平基因多效性检验验证结果的稳定性和可靠性。结果分析发现CCL25的P值为0.040(OR=1.331,95%CI:1.014~1.747),CD40的P值为0.040(OR=1.677,95%CI:1.025~2.744),IL-17C的P值为0.013,(OR=0.480,95%CI:0.269~0.858),结果具有统计学意义。结论 CCL25、CD40均能够增加TD的患病风险,IL-17C能够降低TD的患病风险。

关键词: 抽动障碍, 炎性因子, 孟德尔随机化, 因果关系

CLC Number:

R179

ZHANG Lili, SHANG Lili, CUI Heqing, ZHOU Bingyuan, WU Anqi. Mendelian randomization study on the relationship between inflammatory circulation factors and the risk of tic disorder[J]. Chinese Journal of Child Health Care, 2025, 33(11): 1261-1269.

张莉莉, 尚莉丽, 崔何晴, 周冰原, 吴安琪. 基于孟德尔随机化研究分析炎性循环因子与抽动障碍发病风险的关系[J]. 中国儿童保健杂志, 2025, 33(11): 1261-1269.

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