线粒体DNA拷贝数与孤独症谱系障碍的因果关系  

Causal relationship between mitochondrial DNA copy number and autism spectrum disorders

作　　者：黄燕 李渊龙 HUANG Yan;LI Yuan-long(Department of Child Health,Hainan Women and Children's Medical Center,Haikou 571100,Hainan,CHINA)

机构地区：[1]海南省妇女儿童医学中心儿童保健科,海南海口571100

出　　处：《海南医学》2025年第7期934-938,共5页Hainan Medical Journal

基　　金：海南省临床医学中心建设项目(编号:琼卫医函[2021]75号)。

摘　　要：目的探究线粒体DNA(mtDNA)拷贝数与孤独症谱系障碍(ASD)之间的双向因果关系。方法采用两样本孟德尔随机化(mendelian randomization,MR)研究方法使用公开可访问的全基因组关联研究数据(GWAS)进行双样本双向MR分析。mtDNA拷贝数以及ASD的GWAS数据均提取自IEU Open GWAS数据库,利用R语言软件(4.3.2版)及Two SampleMR包进行MR分析。主要分析法采用逆方差加权法(inverse variance weighted,IVW),补充分析法采用将加权中位数、MR-Egger回归法、中位模型;并采用异质性检验、水平多效性检验、留一法等对结果进行敏感性分析。结果IVW支持线粒体DNA拷贝数减少与ASD风险增加存在因果关系(OR=0.735,95%CI:0.597~0.905,P=0.003);加权中位数、MR-Egger回归法、中位模型的结果与IVW结果方向一致;敏感性分析提示研究结果不具有水平多效性和异质性,结果稳定。结论线粒体DNA拷贝数与ASD存在因果关系,线粒体DNA拷贝数减少可能是导致ASD发病的潜在遗传危险因素之一。Objective To explore the bidirectional causal relationship between mitochondrial DNA copy number and autism spectrum disorder(ASD).Methods A two-sample Mendelian randomization(MR)study was conducted using publicly available genome-wide association study(GWAS)data for bidirectional MR analysis.The GWAS data for mtDNA copy number and ASD were extracted from the IEU Open GWAS database,and MR analysis was performed using R software(version 4.3.2)with the TwoSampleMR package.The primary analysis method was inverse variance weighting(IVW),supplemented by weighted median,MR-Egger regression,and median models.Sensitivity analyses,including heterogeneity testing,horizontal pleiotropy testing,and leave-one-out analysis,were conducted to validate the results.Results IVW supported a causal relationship between reduced mtDNA copy number and increased ASD risk(OR=0.735,95%CI:0.597-0.905,P=0.003).The results of the weighted median,MR-Egger regression,and median models were consistent with the IVW results.Sensitivity analyses indicated no horizontal pleiotropy or heterogeneity,confirming the stability of the results.Conclusion There is a causal relationship between mitochondrial DNA copy number and ASD.The reduction of mitochondrial DNA copy number may be one of the potential genetic risk factors for ASD.

关 键 词：孤独症谱系障碍 线粒体DNA拷贝数 孟德尔随机化 全基因组关联研究 

分 类 号：R729[医药卫生—儿科]