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. 2021 Jul 9;50(3):817-828.
doi: 10.1093/ije/dyaa183.

Is disrupted sleep a risk factor for Alzheimer's disease? Evidence from a two-sample Mendelian randomization analysis

Emma L Anderson  1   2 , Rebecca C Richmond  1   2 , Samuel E Jones  3 , Gibran Hemani  1   2 , Kaitlin H Wade  1   2 , Hassan S Dashti  4   5 , Jacqueline M Lane  4   5   6 , Heming Wang  5   7 , Richa Saxena  4   5   6   7 , Ben Brumpton  1   8   9 , Roxanna Korologou-Linden  1   2 , Jonas B Nielsen  10 , Bjørn Olav Åsvold  8   11 , Gonçalo Abecasis  10 , Elizabeth Coulthard  12 , Simon D Kyle  13 , Robin N Beaumont  3 , Jessica Tyrrell  3 , Timothy M Frayling  3 , Marcus R Munafò  1   14 , Andrew R Wood  3 , Yoav Ben-Shlomo  2 , Laura D Howe  1   2 , Deborah A Lawlor  1   2 , Michael N Weedon  3 , George Davey Smith  1   2
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Is disrupted sleep a risk factor for Alzheimer's disease? Evidence from a two-sample Mendelian randomization analysis

Emma L Anderson et al. Int J Epidemiol. .

Abstract

Background: It is established that Alzheimer's disease (AD) patients experience sleep disruption. However, it remains unknown whether disruption in the quantity, quality or timing of sleep is a risk factor for the onset of AD.

Methods: We used the largest published genome-wide association studies of self-reported and accelerometer-measured sleep traits (chronotype, duration, fragmentation, insomnia, daytime napping and daytime sleepiness), and AD. Mendelian randomization (MR) was used to estimate the causal effect of self-reported and accelerometer-measured sleep parameters on AD risk.

Results: Overall, there was little evidence to support a causal effect of sleep traits on AD risk. There was some suggestive evidence that self-reported daytime napping was associated with lower AD risk [odds ratio (OR): 0.70, 95% confidence interval (CI): 0.50-0.99). Some other sleep traits (accelerometer-measured 'eveningness' and sleep duration, and self-reported daytime sleepiness) had ORs of a similar magnitude to daytime napping, but were less precisely estimated.

Conclusions: Overall, we found very limited evidence to support a causal effect of sleep traits on AD risk. Our findings provide tentative evidence that daytime napping may reduce AD risk. Given that this is the first MR study of multiple self-report and objective sleep traits on AD risk, findings should be replicated using independent samples when such data become available.

Keywords: Alzheimer’s disease; Mendelian randomization; Sleep; causal inference; dementia.

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Figures

Figure 1
Figure 1
Flow chart detailing data sources for each analysis performed. AD, Alzheimer’s disease; GWAS, genome-wide association study; MR, Mendelian randomization; IGAP, International Genomics of Alzheimer’s Project; IVW, Inverse Variance Weighted; PGC, Psychiatric Genomics Consortium; ADSP, Alzheimer’s Disease Sequencing Project
Figure 2
Figure 2
Associations of sleep traits with Alzheimer’s Disease. Note that the MR Egger estimate for the effect of daytime sleepiness was not plotted due to imprecision. IVW, Inverse Variance Weighted
Figure 3
Figure 3
Comparing results for associations of sleep traits on risk of Alzheimer’s disease (AD) when using the International Genomics of Alzheimer’s Project (IGAP) genome-wide association study (GWAS) alone (n = 17 008 AD cases and 37 154 controls; IGAP) vs the GWAS meta-analysis of IGAP, the AD working group of the Psychiatric Genomics Consortium and the AD Sequencing Project (n = 24 087 cases and 55 058 controls: META data). Note that the MR Egger estimate for effect of accelerometer-measured sleep fragmentation using IGAP data was not plotted due to imprecision. MR, Mendelian randomization; AM, accelerometer-measured; SR, self-report
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