Sleep advances : a journal of the Sleep Research Society · 2026
Shared genetic architecture between Parkinson's disease and self-reported sleep-related traits implicates the MAPT locus on chromosome 17.
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Aguilar-Roldán Aura, Ogonowski Natalia S, Rentería Miguel E, García-Marín Luis M
Аннотация
STUDY OBJECTIVES: Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms. Among the latter, sleep disturbances are particularly common and include insomnia, obstructive sleep apnea (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 analyzed genome-wide association study (GWAS) summary statistics for PD (~37.7 K cases, ~18.6 K proxy cases, ~1.4 M controls) and eight self-reported sleep-related traits (each with n > 300 000): ease of getting up, chronotype (morningness), napping, insomnia, OSA, snoring, daytime dozing, and sleep duration. Genetic correlations were estimated using Linkage Disequilibrium (LD) score regression, and GWAS-pairwise analysis was used to identify genomic segments harboring 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 (p < .05). A separate, local-level analysis identified six genomic regions harboring 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 remodeling. Our results highlight sleep disturbances as a potential early marker or risk factor of PD.
METHODS: We analyzed genome-wide association study (GWAS) summary statistics for PD (~37.7 K cases, ~18.6 K proxy cases, ~1.4 M controls) and eight self-reported sleep-related traits (each with n > 300 000): ease of getting up, chronotype (morningness), napping, insomnia, OSA, snoring, daytime dozing, and sleep duration. Genetic correlations were estimated using Linkage Disequilibrium (LD) score regression, and GWAS-pairwise analysis was used to identify genomic segments harboring 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 (p < .05). A separate, local-level analysis identified six genomic regions harboring 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 remodeling. Our results highlight sleep disturbances as a potential early marker or risk factor of PD.