Sleep, major depressive disorder, and Alzheimer disease: A Mendelian randomization study

Jian Huang; Verena Zuber; Paul M Matthews; Paul Elliott; Joanna Tzoulaki; Abbas Dehghan

doi:10.1212/WNL.0000000000010463

Sleep, major depressive disorder, and Alzheimer disease: A Mendelian randomization study

Neurology. 2020 Oct 6;95(14):e1963-e1970. doi: 10.1212/WNL.0000000000010463. Epub 2020 Aug 19.

Authors

Jian Huang¹, Verena Zuber¹, Paul M Matthews¹, Paul Elliott¹, Joanna Tzoulaki¹, Abbas Dehghan²

Affiliations

¹ From the MRC Centre for Environment and Health (J.H., V.Z., P.E., J.T., A.D.), Department of Epidemiology and Biostatistics, School of Public Health, St. Mary's Campus, Imperial College London, Norfolk Place; UK Dementia Research Institute at Imperial College London (J.H., P.M.M., J.T., A.D.); Imperial College NIHR Biomedical Research Centre (J.H., P.E.); Department of Brain Sciences (P.M.M., P.E.), Faculty of Medicine, Imperial College London; Health Data Research UK-London; and Department of Hygiene and Epidemiology (P.E., J.T.), University of Ioannina Medical School, Greece.
² From the MRC Centre for Environment and Health (J.H., V.Z., P.E., J.T., A.D.), Department of Epidemiology and Biostatistics, School of Public Health, St. Mary's Campus, Imperial College London, Norfolk Place; UK Dementia Research Institute at Imperial College London (J.H., P.M.M., J.T., A.D.); Imperial College NIHR Biomedical Research Centre (J.H., P.E.); Department of Brain Sciences (P.M.M., P.E.), Faculty of Medicine, Imperial College London; Health Data Research UK-London; and Department of Hygiene and Epidemiology (P.E., J.T.), University of Ioannina Medical School, Greece. a.dehghan@imperial.ac.uk.

Abstract

Objective: To explore the causal relationships between sleep, major depressive disorder (MDD), and Alzheimer disease (AD).

Methods: We conducted bidirectional 2-sample Mendelian randomization analyses. Genetic associations were obtained from the largest genome-wide association studies currently available in UK Biobank (n = 446,118), Psychiatric Genomics Consortium (n = 18,759), and International Genomics of Alzheimer's Project (n = 63,926). We used the inverse variance-weighted Mendelian randomization method to estimate causal effects and weighted median and Mendelian randomization-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 adjustment 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 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / epidemiology*
Alzheimer Disease / genetics
Depressive Disorder, Major / epidemiology*
Depressive Disorder, Major / genetics
Female
Genome-Wide Association Study
Humans
Male
Mendelian Randomization Analysis
Phenotype
Sleep* / genetics

Abstract

Publication types

MeSH terms

Grants and funding