孟德尔随机化
计时型
全基因组关联研究
医学
内科学
疾病
肌萎缩侧索硬化
心理学
肿瘤科
早晨
单核苷酸多态性
基因型
生物
遗传学
基因
遗传变异
作者
Nàtalia Cullell,Jara Cárcel‐Márquez,Cristina Gallego‐Fabrega,Elena Muiño,Laia Llucià‐Carol,Miquel Lledós,Karol Enrique Uscamaita Amaut,Jerzy Krupiński,Israel Fernández‐Cadenas
标识
DOI:10.1016/j.neurobiolaging.2021.05.008
摘要
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 Genome-Wide Association Study (GWAS) to evaluate their causal relationship with the ND risk through Inverse-Variance 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 = 8.47×10-09 and 95%CI:-7.28 to -4.44, p = 5.87×10-16, 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.
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