Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects
Krohn, Lynne ; Brolin, Kajsa LU
and Gan-Or, Ziv
(2022)
In Nature Communications
13(1).
- 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... (More)
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.
(Less)
- author
- Krohn, Lynne
; Brolin, Kajsa
LU
and Gan-Or, Ziv
- author collaboration
- organization
- publishing date
- 2022-12
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Communications
- volume
- 13
- issue
- 1
- article number
- 7496
- pages
- 16 pages
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:36470867
- scopus:85143480320
- ISSN
- 2041-1723
- DOI
- 10.1038/s41467-022-34732-5
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2022, The Author(s).
- id
- ab9c7862-2d73-4f9c-9c01-72b2d1bd8cb0
- date added to LUP
- 2022-12-17 08:00:07
- date last changed
- 2024-04-18 08:19:05
@article{ab9c7862-2d73-4f9c-9c01-72b2d1bd8cb0,
abstract = {{<p>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.</p>}},
author = {{Krohn, Lynne and Brolin, Kajsa and Gan-Or, Ziv}},
issn = {{2041-1723}},
language = {{eng}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Nature Communications}},
title = {{Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects}},
url = {{http://dx.doi.org/10.1038/s41467-022-34732-5}},
doi = {{10.1038/s41467-022-34732-5}},
volume = {{13}},
year = {{2022}},
}