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

Article type: Research Article

Authors: Wei, Tao^{a; 1} | Guo, Zheng^{b; 1} | Wang, Zhibin^a | Li, Cancan^c | Zhu, Wei^a | Zheng, Yulu^b | Yin, Yunsi^a | Mi, Yingxin^a | Xia, Xinyi^a | Hou, Haifeng^{b; c} | Tang, Yi^{a; d; *}

Affiliations: [a] Innovation Center for Neurological Disorders, Department of Neurology, Xuanwu Hospital, Capital Medical | [b] Centre for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Perth, 8 Australia | [c] School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian China | [d] Neurodegenerative Laboratory of Ministry of Education of the People’s Republic of China, Beijing, China

Correspondence: [*] Correspondence to: Yi Tang, Department of Neurology & Innovation Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing 100053, China. Tel.: +86 1083199456; Fax: +86 10 83171070; E-mail: tangyi@xwhosp.org.

Note: [1] These authors contributed equally to this work.

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

DOI: 10.3233/JAD-220010

Journal: Journal of Alzheimer's Disease, vol. 87, no. 2, pp. 675-684, 2022