两样本孟德尔随机化分析研究肠道微生物与阿尔兹海默症之间的关系-现代医学

两样本孟德尔随机化分析研究肠道微生物与阿尔兹海默症之间的关系

作者：俞柏竹¹ 陈军磊² 张振国² 王婧怡² 王维浩² 苏文博² 丁图南³ 陈艳³ 张喜武⁴ 窦金金⁵

单位：1. 黑龙江中医药大学药学院, 黑龙江哈尔滨 150006;
2. 黑龙江中医药大学第一临床医学院, 黑龙江哈尔滨 150006;
3. 北京中医药大学中医学院, 北京 100007;
4. 黑龙江中医药大学实验实训中心, 黑龙江哈尔滨 150006;
5. 黑龙江中医药大学附属第一医院, 黑龙

关键词：孟德尔随机化肠道微生物阿尔兹海默症

分类号：R741;R749.3

出版年·卷·期（页码）：2023·51·第十一期（1532-1539）

摘要：

目的：利用两样本孟德尔随机化探究271种肠道微生物与阿尔兹海默症(AD)的因果关系。方法：采用公共数据库中FIRISK2022研究的肠道微生物全基因组关联研究(GWAS)数据(n=5 959)和精神疾病全基因组研究联盟的精神分裂症GWAS数据(n=35 802)，根据预设的阈值提取与 271种肠微生物相对丰度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(IVW)进行分析，根据效应指标优势比(OR)和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等来验证结果的稳定性和可靠性。结果：Defiluviileaccae科丰度的升高，可能增加AD的患病风险(OR=1.181,95%CI 1.018~1.37)。留一法分析显示结果稳定，不存在对结果有强影响的工具变量，该因果关系方向为正向，且可以剔除异质性和水平基因多效性对因果效应估计产生的影响。结论：Defiluviileaccae科肠道菌群可能会升高AD的患病风险，并且Ruminococcusgnavus菌群是AD缓解的重要因素。

Objective: To explore the causal relationship between 271 gastrointestinal microbiomes and Alzheimer's disease by using two-sample Mendelian randomization(TSMR) analysis.Methods: Gastrointestinal microbiome genome-wide association studies(GWAS)data(n=5 959) of the FIRISK2022's study in the public database and the schizophrenia GWAS data of the Psychiatric Genomics Consortium(n=35 802) were used to conduct the study. According to the preset threshold, independent genetic loci significantly related to the relative abundance of 271 intestinal microorganisms were extracted as instrumental variables. The inverse-variance weighting method(IVW)was employed to perform the analysis and the results were evaluated according to the effect index odds ratio(OR) and 95% confidence interval. Leave-one-out method, heterogeneity test, horizontal gene pleiotropy test, etc. were used to verify the stability and reliability of the results. Results: The increase in the abundance of the Defiluvileaccae family increased the risk of Alzheimer's disease(OR=1.181(95%CI:1.018-1.37). Leave-one-out analysis showed that the results were stable and no instrumental variables strongly impacted on the results.The results showed thatthe gastrointestinal microbiomes were positively related to Alzheimer's disease.The influence of heterogeneity and horizontal pleiotropy on the estimation of causal effect could be eliminated.Conclusion: Defiluviileaccae family increases the risk of Alzheimer's disease and Ruminococcus gnavus group is an important factor in AD remission.

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