Sleep behaviors and Parkinson?s disease: A bidirectional Mendelian randomization analysis

Objective: Whether the quantity and quality of sleep are the risk factors for the development of Parkinson's disease remains unclear though it has now been confirmed that the quality of sleep among patients with Par-kinson's disease is affected at the prodromal and clinical stages. Accordingly, this study aimed to examine the bidirectional causal relationships of multiple sleep-related phenotypes with Parkinson's disease using a two-sample Mendelian randomization (MR) method. Methods: The summary-level data collected from the published genome-wide association studies was used for analysis. Besides, the genetic relationships between different sleep-related phenotypes, including self-reported and accelerometer measured traits, were estimated for the risk and age at the onset of Parkinson's disease. To conduct MR analysis, inverse variance weighted, weight median, MR-Egger, and MR-PRESSO method were mainly used. Moreover, sensitivity analyses were carried out to examine the pleiotropic effect. Results: In general, there was insufficient evidence to support the causal effect of sleep-related phenotypes on risk (N cases/controls = 33,674/449,056) and age at the onset (N cases = 28,568) of Parkinson's disease. However, the results of this study indicated that the later onset age of Parkinson's disease was related to the frequent occurrence of insomnia (OR [95% CI] 1.007 [1.003, 1.011], P < 0.001) after the adjustment for multiple testing. Conclusions: The results of this study suggest that insomnia-associated single nucleotide polymorphisms are more frequent in later onset Parkinson's disease patients compared to earlier onset patients. However, given the limitations of statistical power and potential bias, further validation should be still conducted through larger population research.