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

Emma L. Anderson; Rebecca C. Richmond; Samuel E. Jones; Gibran Hemani; Kaitlin H. Wade; Hassan S. Dashti; Jacqueline M. Lane; Heming Wang; Richa Saxena; Ben Brumpton; Roxanna Korologou-Linden; Jonas B. Nielsen; Bjørn Olav Åsvold; Goncąlo Abecasis; Elizabeth Coulthard; Simon D. Kyle; Robin N. Beaumont; Jessica Tyrrell; Timothy M. Frayling; Marcus R. Munafò; Andrew R. Wood; Yoav Ben-Shlomo; Laura D. Howe; Deborah A. Lawlor; Michael N. Weedon; George Davey Smith

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, Rebecca C. Richmond, Samuel E. Jones, Gibran Hemani, Kaitlin H. Wade, Hassan S. Dashti, Jacqueline M. Lane, Heming Wang, Richa Saxena, Ben Brumpton, Roxanna Korologou-Linden, Jonas B. Nielsen, Bjørn Olav Åsvold, Goncąlo Abecasis, Elizabeth Coulthard, Simon D. Kyle, Robin N. Beaumont, Jessica Tyrrell, Timothy M. Frayling, Marcus R. MunafòAndrew R. Wood, Yoav Ben-Shlomo, Laura D. Howe, Deborah A. Lawlor, Michael N. Weedon, George Davey Smith

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32 Citations (SciVal)

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.

Original language	English
Pages (from-to)	817-828
Number of pages	12
Journal	International Journal of Epidemiology
Volume	50
Issue number	3
Early online date	11 May 2020
DOIs	https://doi.org/10.1093/ije/dyaa183
Publication status	Published - 1 Jun 2021

Keywords

Alzheimer's disease
causal inference
dementia
Mendelian randomization
Sleep

ASJC Scopus subject areas

Epidemiology

Access to Document

10.1093/ije/dyaa183Licence: CC BY

Cite this

Anderson, E. L., Richmond, R. C., Jones, S. E., Hemani, G., Wade, K. H., Dashti, H. S., Lane, J. M., Wang, H., Saxena, R., Brumpton, B., Korologou-Linden, R., Nielsen, J. B., Åsvold, B. O., Abecasis, G., Coulthard, E., Kyle, S. D., Beaumont, R. N., Tyrrell, J., Frayling, T. M., ... Davey Smith, G. (2021). Is disrupted sleep a risk factor for Alzheimer's disease? Evidence from a two-sample Mendelian randomization analysis. International Journal of Epidemiology, 50(3), 817-828. https://doi.org/10.1093/ije/dyaa183

Anderson, EL, Richmond, RC, Jones, SE, Hemani, G, Wade, KH, Dashti, HS, Lane, JM, Wang, H, Saxena, R, Brumpton, B, Korologou-Linden, R, Nielsen, JB, Åsvold, BO, Abecasis, G, Coulthard, E, Kyle, SD, Beaumont, RN, Tyrrell, J, Frayling, TM, Munafò, MR, Wood, AR, Ben-Shlomo, Y, Howe, LD, Lawlor, DA, Weedon, MN & Davey Smith, G 2021, 'Is disrupted sleep a risk factor for Alzheimer's disease? Evidence from a two-sample Mendelian randomization analysis', International Journal of Epidemiology, vol. 50, no. 3, pp. 817-828. https://doi.org/10.1093/ije/dyaa183

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

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, causal inference, dementia, Mendelian randomization, Sleep",

author = "Anderson, {Emma L.} and Richmond, {Rebecca C.} and Jones, {Samuel E.} and Gibran Hemani and Wade, {Kaitlin H.} and Dashti, {Hassan S.} and Lane, {Jacqueline M.} and Heming Wang and Richa Saxena and Ben Brumpton and Roxanna Korologou-Linden and Nielsen, {Jonas B.} and {\AA}svold, {Bj{\o}rn Olav} and Gonc{\c a}lo Abecasis and Elizabeth Coulthard and Kyle, {Simon D.} and Beaumont, {Robin N.} and Jessica Tyrrell and Frayling, {Timothy M.} and Munaf{\`o}, {Marcus R.} and Wood, {Andrew R.} and Yoav Ben-Shlomo and Howe, {Laura D.} and Lawlor, {Deborah A.} and Weedon, {Michael N.} and {Davey Smith}, George",

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doi = "10.1093/ije/dyaa183",

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T1 - Is disrupted sleep a risk factor for Alzheimer's disease?

T2 - Evidence from a two-sample Mendelian randomization analysis

AU - Anderson, Emma L.

AU - Richmond, Rebecca C.

AU - Jones, Samuel E.

AU - Hemani, Gibran

AU - Wade, Kaitlin H.

AU - Dashti, Hassan S.

AU - Lane, Jacqueline M.

AU - Wang, Heming

AU - Saxena, Richa

AU - Brumpton, Ben

AU - Korologou-Linden, Roxanna

AU - Nielsen, Jonas B.

AU - Åsvold, Bjørn Olav

AU - Abecasis, Goncąlo

AU - Coulthard, Elizabeth

AU - Kyle, Simon D.

AU - Beaumont, Robin N.

AU - Tyrrell, Jessica

AU - Frayling, Timothy M.

AU - Munafò, Marcus R.

AU - Wood, Andrew R.

AU - Ben-Shlomo, Yoav

AU - Howe, Laura D.

AU - Lawlor, Deborah A.

AU - Weedon, Michael N.

AU - Davey Smith, George

PY - 2021/6/1

Y1 - 2021/6/1

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - causal inference

KW - dementia

KW - Mendelian randomization

KW - Sleep

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JO - International Journal of Epidemiology

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