Five major psychiatric disorders and Alzheimer's disease: A bidirectional mendelian randomization study

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.

Keywords

Alzheimer's disease, causality, genetic association, Mendelian randomization, psychiatric disorders

Document Type

Journal Article

Date of Publication

1-1-2022

Volume

87

Issue

2

PubMed ID

35367968

Publication Title

Journal of Alzheimer's Disease

Publisher

IOS Press

School

Centre for Precision Health / School of Medical and Health Sciences

RAS ID

52012

Funders

Beijing Natural Science Foundation (JQ19024) National Natural Science Foundation of China (81970996) National Key R&D Program of China (2017YFC1310102 and 2019YFC0118200) Beijing Municipal Science & Technology Commission (Z191100006619046) Edith Cowan University Higher Degree by Research Scholarship (ECU-HDR ST10469322 and ST10468211) Edith Cowan University - Centre for Precision Health HDR Student Award ECU (2021-02406-GUO)

Grant Number

ECU-HDR ST10469322 ST10468211 2021-02406-GUO

Comments

Wei, T., Guo, Z., Wang, Z., Li, C., Zhu, W., Zheng, Y., ... & Tang, Y. (2022). Five Major Psychiatric Disorders and Alzheimer’s Disease: A Bidirectional Mendelian Randomization Study. Journal of Alzheimer's Disease, 87(2), pp. 675-684. https://doi.org/10.3233/JAD-220010

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First Page

675

Last Page

684

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Link to publisher version (DOI)

10.3233/JAD-220010