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

Journal article

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

Authors: Krohn, L; Heilbron, K; Blauwendraat, C; Reynolds, RH; Yu, E

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Nature Communications
• Volume: 13
• Issue: 1
• Pages: 7496-7496
• Article number: 7496
• Publication date: 2022-12-05
• DOI: 10.1038/s41467-022-34732-5
• EISSN: 2041-1723
• ISSN: 2041-1723
• Language: English
• Keywords: Internal medicine; Gene; Polygenic risk score; Genome-wide association study; Bioinformatics; Genetics; Genetic association; Biology; Genotype; Alpha-synuclein; Phenotype; Synucleinopathies; Disease; Single-nucleotide polymorphism; Sleep (system call); Genetic architecture; Medicine; Neuroscience