ABSTRACT Study Objectives Parkinson’s disease (PD) is a neurodegenerative disorder characterised by motor and non-motor symptoms. Among the latter, sleep disturbances are particularly common and include insomnia, obstructive sleep apnoea (OSA), and excessive daytime sleepiness. Here, we investigated the shared genetic architecture between PD and sleep-related traits to uncover biological pathways that underpin this relationship. Methods We analysed genome-wide association study (GWAS) summary statistics for PD (~37.7K cases, ~18.6K proxy cases, ~1.4M controls) and eight self-reported sleep-related traits (each with n300,000): ease of getting up, chronotype (morningness), napping, insomnia, OSA, snoring, daytime dozing, and sleep duration. Genetic correlations were estimated using LD score regression, and GWAS-Pairwise analysis was used to identify genomic segments harbouring shared causal variants. We then mapped these variants to protein-coding genes. Results We observed a genome-wide genetic correlation between PD and daytime dozing (P0.05). A separate, local-level analysis identified six genomic regions harbouring shared causal variants between PD and other sleep-related traits (primarily ease of getting up and napping). The most statistically significant of these local associations was observed at a single locus on chromosome 17, which contains the majority of mapped protein-coding genes, including ARHGAP27, PLEKHM1, CRHR1, and MAPT. These genes are implicated in neurodegeneration and circadian rhythm regulation. Conclusions These findings suggest that the MAPT locus, beyond its established role in PD, may also contribute to sleep-wake regulation via shared biological pathways, including tau pathology, stress response, and chromatin remodelling. Our results highlight sleep disturbances as a potential early marker or risk factor of Parkinson’s disease.
Aguilar-Roldán et al. (Thu,) studied this question.