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: OR_ADHD, 1.030, 95% CI, 0.908–1.168, p = 0.674; OR_{anxiety disorders}, 0.904, 95% CI, 0.722–1.131, p = 0.377; OR_ASD, 0.973, 95% CI, 0.746–1.272, p = 0.846; OR_BIP, 1.033, 95% CI, 0.925–1.153, p = 0.564; and OR_{schizophrenia}, 1.039, 95% CI, 0.986–1.095, p = 0.156; reverse IVW: OR_ADHD, 0.993, 95% CI, 0.954–1.034, p = 0.746; OR_{anxiety disorders}, 1.000, 95% CI, 0.999–1.000, p = 0.898; OR_ASD, 1.001, 95% CI, 0.962–1.042, p = 0.949; OR_BIP, 0.997, 95% CI, 0.966–1.028, p = 0.831; and OR_{schizophrenia}, 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.