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.
Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects / Krohn, L., Heilbron, K., Blauwendraat, C., Reynolds, R.H., Yu, E., Senkevich, K., Rudakou, U., Estiar, M.A., Gustavsson, E.K., Brolin, K., Ruskey, J.A., Freeman, K., Asayesh, F., Chia, R., Arnulf, I., M. T. M., H.u., Montplaisir, J.Y., Gagnon, J.-F., Desautels, A., Dauvilliers, Y., et al.. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 13:1(2022). [10.1038/s41467-022-34732-5]
Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects
Ferini-Strambi L.;
2022-01-01
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.| File | Dimensione | Formato | |
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