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

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