免疫细胞介导的DNA拷贝数与阿尔茨海默病的因果关系:孟德尔随机化研究
Immune cell-mediated causal relationship between DNA copy number and Alzheimer disease:a Mendelian randomization study
朱赟 1魏佳明 1曾逸笛 1林瑞芳 1刘泳君 1郭志华2
作者信息
- 1. 湖南中医药大学中医学院(长沙 410208)
- 2. 湖南中医药大学中医学院(长沙 410208);湖南中医药大学第一中医临床学院(长沙 410208);湖南中医药大学慢病中医智能诊断与治未病湖南省普通高等学校重点实验室(长沙 410208);互联网+慢病中医诊治与养生智能化应用研究生联合培养基地(长沙 410208)
- 折叠
摘要
目的 利用孟德尔随机化(Mendelian randomization,MR)方法探讨DNA拷贝数与阿尔茨海默病风险之间的因果关系及免疫细胞的潜在中介效应.方法 从全基因组关联分析数据库中获取了 731种免疫细胞、DNA拷贝数、阿尔茨海默病的相关数据,主要采用逆方差加权方法及MR-Egger法,对DNA拷贝数与阿尔茨海默病的因果关系进行双向MR分析.此外,通过两步中介分析识别出可能的中介免疫细胞.结果 筛选后共纳入134个SNP进行双向MR分析.MR分析结果显示,DNA拷贝数与阿尔茨海默病风险之间存在负向因果关系(P＜0.05),而反向分析无统计学意义(P＞0.05),敏感性分析验证了结果的稳定性.中介分析显示免疫细胞表型HVEM on CD45RA-CD4+在DNA拷贝数与阿尔茨海默病风险之间的因果关系中起到部分中介作用(中介效应比为4.6％).结论 DNA拷贝数的增加可能会降低阿尔茨海默病风险,免疫细胞在这一因果联系中存在部分中介作用.
Abstract
Objective To explore the causal relationship between DNA copy number and the risk of Alzheimer disease(AD)using Mendelian randomization(MR)methods,as well as to investigate the potential mediating effects of immune cells.Methods The data related to 731 immune cell types,DNA copy number and AD from the Genome-Wide Association Study database were collected.A bidirectional MR analysis was conducted to explore the causal relationship between DNA copy number and AD,primarily using the inverse-variance weighted method and MR-Egger method.Additionally,a two-step mediation analysis was performed to identify potential mediating immune cells.Results A total of 134 single-nucleotide polymorphisms were included for bidirectional MR analysis.The MR methods results showed a negative causal relationship between DNA copy number and the risk of AD(P＜0.05),while the reverse analysis showed no statistical significance.Sensitivity analysis confirmed the robustness of these results.The mediation analysis indicated that the immune cell phenotype(HVEM on CD45RA-CD4+)partially mediated the causal relationship between DNA copy numbers and the risk of AD,with a mediation effect proportion of 4.6％.Conclusion An increase in DNA copy numbers may reduce the risk of AD,and immune cells partially mediate this causal relationship.
关键词
DNA拷贝数/免疫细胞/阿尔茨海默病/孟德尔随机化/中介Key words
DNA copy number/immune cells/Alzheimer disease/Mendelian randomization/mediation引用本文复制引用
基金项目
湖南省教育厅科研项目(23A0308)
湖南省教育厅科研项目(23A0310)
湖南省教育厅科研项目(23C0162)
湖南中医药大学本科生科研创新基金(223BKS017)
出版年
2024
NETL
NSTL
万方数据