Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects

Lynne Krohn; Kajsa Brolin; Ziv Gan-Or; 23andMe Research Team

doi:10.1038/s41467-022-34732-5

Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects

Lynne Krohn, Kajsa Brolin, Ziv Gan-Or, 23andMe Research Team

McGill University

Research output: Contribution to journal › Article › peer-review

Abstract

Rapid-eye movement (REM) sleep behavior disorder (RBD), enactment of dreams during REM sleep, is an early clinical symptom of alpha-synucleinopathies and defines a more severe subtype. The genetic background of RBD and its underlying mechanisms are not well understood. Here, we perform a genome-wide association study of RBD, identifying five RBD risk loci near SNCA, GBA, TMEM175, INPP5F, and SCARB2. Expression analyses highlight SNCA-AS1 and potentially SCARB2 differential expression in different brain regions in RBD, with SNCA-AS1 further supported by colocalization analyses. Polygenic risk score, pathway analysis, and genetic correlations provide further insights into RBD genetics, highlighting RBD as a unique alpha-synucleinopathy subpopulation that will allow future early intervention.

Original language	English
Article number	7496
Number of pages	16
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-34732-5
Publication status	Published - 2022 Dec

Bibliographical note

Publisher Copyright:
© 2022, The Author(s).

Subject classification (UKÄ)

Medical Genetics
Neurosciences

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10.1038/s41467-022-34732-5Licence: CC BY

1 Doctoral Thesis (compilation)

The etiology of Parkinson's disease. Genetic and non-genetic risk factors for a multifactorial disease
Brolin, K., 2023, Lund: Lund University, Faculty of Medicine. 118 p.
Research output: Thesis › Doctoral Thesis (compilation)

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Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects

Abstract

Bibliographical note

Subject classification (UKÄ)

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Research output

The etiology of Parkinson's disease. Genetic and non-genetic risk factors for a multifactorial disease

Cite this