Sleep/wake cycle alterations as a cause of neurodegenerative diseases: a mendelian randomization study
Por:
Cullell, N, Carcel-Marquez, J, Gallego-Fabrega, C, Muino, E, Llucia-Carol, L, Lledos, M, Amaut, KEU, Krupinski, J, Fernandez-Cadenas, I
Publicada:
1 oct 2021
Ahead of Print:
1 ago 2021
Resumen:
Sleep and/or wake cycle alterations are common in neurodegenerative diseases (ND). Our aim was to determine whether there is a causal relationship between sleep and/or wake cycle patterns and ND (Parkinson's disease (PD) age at onset (AAO), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS)) using two-sample Mendelian Randomization (MR). We selected 12 sleep traits with available GenomeWide Association Study (GWAS) to evaluate their causal relationship with the ND risk through InverseVariance Weighted regression as main analysis. We used as outcome the latest ND GWAS with available summary-statistics: PD-AAO (N = 17,996), AD (N = 21,235) and ALS (N = 40,136). MR results pointed to a causal effect of subjective and objective-measured morning chronotype on later PD-AAO (95%CI:0.33-1.81, p = 8.47x10(-09) and 95%CI:-7.28 to -4.44, p = 5.87x10(-16), respectively). Sleep efficiency was causally associated with a decreased AD risk (95%CI:-20.408 to -0.66, p = 0.04) and daytime sleepiness with an increased ALS risk (95%CI:0.15 to 1.61, p = 0.01). Our study suggests that sleep and/or wake patterns have causal relationship with ND. Given that sleep and/or wake patterns are modifiable risk factors, sleep interventions should be investigated as a potential treatment in PD-AAO, AD and ALS. (C) 2021 The Author(s). Published by Elsevier Inc.
Filiaciones:
Cullell, N:
Fundacio Docencia & Recerca MutuaTerrassa, Hosp Univ MutuaTerrassa, Dept Neurol, Terrassa, Spain
St Pau Hosp, Biomed Res Inst St Pau, Stroke Pharmacogen & Genet, Barcelona, Spain
Univ Barcelona, Fac Med, Barcelona, Spain
Carcel-Marquez, J:
St Pau Hosp, Biomed Res Inst St Pau, Stroke Pharmacogen & Genet, Barcelona, Spain
Gallego-Fabrega, C:
Fundacio Docencia & Recerca MutuaTerrassa, Hosp Univ MutuaTerrassa, Dept Neurol, Terrassa, Spain
St Pau Hosp, Biomed Res Inst St Pau, Stroke Pharmacogen & Genet, Barcelona, Spain
Muino, E:
St Pau Hosp, Biomed Res Inst St Pau, Stroke Pharmacogen & Genet, Barcelona, Spain
Llucia-Carol, L:
St Pau Hosp, Biomed Res Inst St Pau, Stroke Pharmacogen & Genet, Barcelona, Spain
Lledos, M:
St Pau Hosp, Biomed Res Inst St Pau, Stroke Pharmacogen & Genet, Barcelona, Spain
Amaut, KEU:
AdSalutem Inst Sleep Med, Barcelona, Spain
Krupinski, J:
Fundacio Docencia & Recerca MutuaTerrassa, Hosp Univ MutuaTerrassa, Dept Neurol, Terrassa, Spain
Manchester Metropolitan Univ, Ctr Biosci, Sch HealthCare Sci, Manchester, Lancs, England
Fernandez-Cadenas, I:
Fundacio Docencia & Recerca MutuaTerrassa, Hosp Univ MutuaTerrassa, Dept Neurol, Terrassa, Spain
St Pau Hosp, Biomed Res Inst St Pau, Stroke Pharmacogen & Genet, Barcelona, Spain
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