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Sleep, major depressive disorder and Alzheimer’s disease: a Mendelian randomisation study

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Title: Sleep, major depressive disorder and Alzheimer’s disease: a Mendelian randomisation study
Authors: Huang, J
Zuber, V
Matthews, P
Tzoulaki, I
Elliott, P
Dehghan, A
Item Type: Journal Article
Abstract: Objective To explore the causal relationships between sleep, major depressive disorder (MDD), and Alzheimer’s disease (AD). Methods We conducted bi-directional two-sample Mendelian randomisation analyses. Genetic associations were obtained from the largest genome-wide association studies currently available in UK Biobank (N=446,118), the Psychiatric Genomics Consortium (N=18,759), and the International Genomics of Alzheimer’s Project (N=63,926). We used the inverse variance weighted Mendelian randomisation method to estimate causal effects, and weighted median and MR-Egger for sensitivity analyses to test for pleiotropic effects. Results We found that higher risk of AD was significantly associated with being a “morning person” (odds ratio (OR)=1.01, P=0.001), shorter sleep duration (self-reported: β=-0.006, P=1.9×10-4; accelerometer-based: β=-0.015, P=6.9×10-5), less likely to report long sleep (β=-0.003, P=7.3×10-7), earlier timing of the least active 5 hours (β=-0.024, P=1.7×10-13), and a smaller number of sleep episodes (β=-0.025, P=5.7×10-14) after adjusting for multiple comparisons. We also found that higher risk of AD was associated with lower risk of insomnia (OR=0.99, P=7×10-13). However, we did not find evidence either that these abnormal sleep patterns were causally related to AD or for a significant causal relationship between MDD and risk of AD. Conclusion We found that AD may causally influence sleep patterns. However, we did not find evidence supporting a causal role of disturbed sleep patterns for AD or evidence for a causal relationship between MDD and AD.
Issue Date: 6-Oct-2020
Date of Acceptance: 23-Apr-2020
URI: http://hdl.handle.net/10044/1/80967
DOI: 10.1212/WNL.0000000000010463
ISSN: 0028-3878
Publisher: American Academy of Neurology
Journal / Book Title: Neurology
Volume: 95
Issue: 14
Copyright Statement: © 2020 American Academy of Neurology.
Sponsor/Funder: Health Data Research Uk
Medical Research Council (MRC)
UK DRI Ltd
Medical Research Council (MRC)
UK DRI Ltd
UK DRI Ltd
Funder's Grant Number: Health Data Research UK
MR/L01341X/1
4050641385
HQR00720
N/A
N/A
Keywords: 1103 Clinical Sciences
1109 Neurosciences
1702 Cognitive Sciences
Neurology & Neurosurgery
Publication Status: Published
Article Number: NEUROLOGY/2019/017517
Online Publication Date: 2020-08-19
Appears in Collections:Faculty of Medicine
School of Public Health
Department of Brain Sciences