五种主要精神障碍与阿尔茨海默病的双向 Mendelian 随机研究。

Five Major Psychiatric Disorders and Alzheimer's Disease: A Bidirectional Mendelian Randomization Study.

机构信息

Innovation Center for Neurological Disorders, Department of Neurology, Xuanwu Hospital, Capital Medical.

Centre for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Perth, 8 Australia.

出版信息

J Alzheimers Dis. 2022;87(2):675-684. doi: 10.3233/JAD-220010.

DOI:10.3233/JAD-220010

PMID:35367968

Abstract

BACKGROUND

Extensive studies put forward the association between Alzheimer's disease (AD) and psychiatric disorders; however, it remains unclear whether these associations are causal.

OBJECTIVE

We aimed to assess the potential causal relationship between major psychiatric disorders and AD.

METHODS

A bidirectional two-sample Mendelian randomization (MR) was applied to evaluate potential causality between five psychiatric disorders and AD by selecting the single-nucleotide polymorphisms from the genome-wide association studies as instrumental variables. Inverse-variance weighted (IVW) method was used as the main analyzing approach to estimate possible causal effects, alternative methods including MR-Egger, the MR pleiotropy residual sum and outlier, and leave-one-out analysis method were implemented as sensitivity analyzing approaches to ensure the robustness of results.

RESULTS

All forward and reverse MR analyses consistently suggested absent causal relations between psychiatric disorders and AD risk [forward IVW: ORADHD, 1.030, 95% CI, 0.908-1.168, p = 0.674; ORanxiety disorders, 0.904, 95% CI, 0.722-1.131, p = 0.377; ORASD, 0.973, 95% CI, 0.746-1.272, p = 0.846; ORBIP, 1.033, 95% CI, 0.925-1.153, p = 0.564; and ORschizophrenia, 1.039, 95% CI, 0.986-1.095, p = 0.156; reverse IVW: ORADHD, 0.993, 95% CI, 0.954-1.034, p = 0.746; ORanxiety disorders, 1.000, 95% CI, 0.999-1.000, p = 0.898; ORASD, 1.001, 95% CI, 0.962-1.042, p = 0.949; ORBIP, 0.997, 95% CI, 0.966-1.028, p = 0.831; and ORschizophrenia, 1.013, 95% CI, 0.978-1.051, p = 0.466].

CONCLUSION

There is no significant evidence supporting the causal association between the five major psychiatric disorders and AD.

摘要

背景

大量研究提出阿尔茨海默病（AD）与精神障碍之间存在关联，但这些关联是否具有因果关系尚不清楚。

目的

我们旨在评估主要精神障碍与 AD 之间的潜在因果关系。

方法

采用双向两样本 Mendelian 随机化（MR）方法，通过选择全基因组关联研究中的单核苷酸多态性作为工具变量，评估五种精神障碍与 AD 之间的潜在因果关系。采用逆方差加权（IVW）法作为主要分析方法来估计可能的因果效应，采用 MR-Egger、MR 多效性残余总和和异常值以及逐一排除分析方法作为敏感性分析方法，以确保结果的稳健性。

结果

所有正向和反向 MR 分析均一致表明，精神障碍与 AD 风险之间不存在因果关系[正向 IVW：ORADHD，1.030，95%CI，0.908-1.168，p=0.674；ORanxiety disorders，0.904，95%CI，0.722-1.131，p=0.377；ORASD，0.973，95%CI，0.746-1.272，p=0.846；ORBIP，1.033，95%CI，0.925-1.153，p=0.564；ORschizophrenia，1.039，95%CI，0.986-1.095，p=0.156；反向 IVW：ORADHD，0.993，95%CI，0.954-1.034，p=0.746；ORanxiety disorders，1.000，95%CI，0.999-1.000，p=0.898；ORASD，1.001，95%CI，0.962-1.042，p=0.949；ORBIP，0.997，95%CI，0.966-1.028，p=0.831；ORschizophrenia，1.013，95%CI，0.978-1.051，p=0.466]。