Relationship between sleep and progression of Parkinson’s disease – A Mendelian randomization study

Background Sleep disturbances are common in Parkinson’s disease (PD) and growing evidence suggests a bidirectional relationship between sleep disruption and neurodegeneration. Objectives To study the causal relationship between sleep and rate of PD progression using two-sample Mendelian randomisation (MR). Methods Genetic variants linked to sleep duration and insomnia were analysed within a GWAS combining 12 longitudinal cohorts of patients with PD(n=4093 patients) examining motor and cognitive progression. Results Genetic liability to insomnia was associated with greater cognitive decline measured by MMSE. Consistent trends across MR estimates suggested a protective effect of increased sleep duration, and detrimental effect of insomnia on motor decline measured using UPDRS-III. Sensitivity analyses reinforced these relationships. The strength of causality among these associations was limited by heterogeneity and balanced pleiotropy. Conclusion Sleep related variables may alter the trajectory of cognitive and motor progression in PD and warrants further study. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement EM was funded by an NHMRC Grant #2008565. EM has received honoraria from the International Movement Disorders Society (MDS) and CSL Seqirus. EM is currently employed by the University of Sydney ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All data used is open-source and obtained from the UK Biobank under their ethics approvals. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes