神经细胞粘附分子-L1与孤独症谱系障碍的两样本孟德尔随机化研究

doi:10.11852/zgetbjzz2024-1405

中国儿童保健杂志 ›› 2025, Vol. 33 ›› Issue (11): 1218-1222.DOI: 10.11852/zgetbjzz2024-1405

神经细胞粘附分子-L1与孤独症谱系障碍的两样本孟德尔随机化研究

蔡明轩, 吴辉文

华中科技大学同济医学院附属湖北妇幼保健院儿童保健科,湖北武汉 430075

收稿日期:2024-11-26 修回日期:2025-03-01 发布日期:2025-11-11 出版日期:2025-11-10
通讯作者: 吴辉文,E-mail:whw0922@163.com
作者简介:蔡明轩(1995—),女,硕士研究生,主要研究方向为儿童神经发育障碍性疾病

Two-sample Mendelian randomization study on the causal associationbetween neural cell adhesion molecule-L1 and autism spectrum disorder

CAI Mingxuan, WU Huiwen

Department of Child Health Care, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430075, China

Received:2024-11-26 Revised:2025-03-01 Online:2025-11-10 Published:2025-11-11
Contact: WU Huiwen, E-mail: whw0922@163.com

摘要/Abstract

摘要： 目的通过孟德尔随机化(MR)方法分析神经细胞粘附分子-L1(NCAM-L1)与孤独症谱系障碍(ASD)之间的因果关系,以期寻找ASD儿童早期识别的生物学标记物。方法选用NCAM-L1的遗传变异作为工具变量,与从公开可用IEU Open GWAS数据库中获得的ASD相关的遗传变异数据集进行两样本MR分析。结果 MR分析后,逆方差加权法结果显示,NCAM-L1与ASD的相对风险呈负相关 (OR=0.933,95%CI:0.829~1.053,P=0.016),加权中位数法也得到相似的结论(OR=0.908,95%CI:0.786~1.034,P=0.046),工具变量不存在水平多效性及异质性。敏感性分析使用留一法和可视化散点图进行,提示研究结果稳健。结论双样本MR分析表明NCAM-L1与ASD存在因果关系,且NCAM-L1水平越低,患ASD的风险越大。

关键词: 孤独症谱系障碍, 神经细胞粘附分子-L1, 孟德尔随机化, 因果关系

Abstract: Objective To analyze the causal relationship between neural cell adhesion molecule-L1 (NCAM-L1) and autism spectrum disorder (ASD) using Mendelian randomization (MR) analysis, in order to identify biological markers for early recognition of ASD in children. Methods Genetic variants of NCAM-L1 were selected as instrumental variables, analyzed in a two-sample MR analysis was performed on the ASD related genetic variation dataset obtained from the publicly available IEU Open GWAS database. Results The MR analysis revealed a negative correlation between NCAM-L1 and the relative risk of ASD using the inverse variance weighted (IVW) method (OR=0.933, 95%CI: 0.829-1.053, P=0.016).A similar association was observed using the weighted median method (OR=0.908, 95%CI: 0.786-1.034, P=0.046).No evidence of horizontal pleiotropy or heterogeneity was detected among the instrumental variables.Sensitivity analysis, including leave-one-out tests and scatterplot visualization, confirmed the robustness of the findings. Conclusion The two-sample MR analysis suggests a causal relationship between NCAM-L1 and ASD, indicating that lower levels of NCAM-L1 are associated with an increased risk of developing ASD.

Key words: autism spectrum disorder, neuronal cell adhesion molecule-L1, Mendelian randomization, causal relationship

中图分类号:

R749.94

蔡明轩, 吴辉文. 神经细胞粘附分子-L1与孤独症谱系障碍的两样本孟德尔随机化研究[J]. 中国儿童保健杂志, 2025, 33(11): 1218-1222.

CAI Mingxuan, WU Huiwen. Two-sample Mendelian randomization study on the causal associationbetween neural cell adhesion molecule-L1 and autism spectrum disorder[J]. Chinese Journal of Child Health Care, 2025, 33(11): 1218-1222.

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神经细胞粘附分子-L1与孤独症谱系障碍的两样本孟德尔随机化研究

Two-sample Mendelian randomization study on the causal associationbetween neural cell adhesion molecule-L1 and autism spectrum disorder

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