Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects.
Lynne KrohnKarl HeilbronCornelis BlauwendraatRegina Hertfelder ReynoldsEric YuKonstantin SenkevichUladzislau RudakouMehrdad A EstiarEmil Karl GustavssonKajsa BrolinJennifer A RuskeyKathryn FreemanFarnaz AsayeshRuth ChiaIsabelle ArnulfMichele T M HuJacques Y MontplaisirJean-François GagnonAlex DesautelsYves DauvilliersGian Luigi GigliMariarosaria ValenteFrancesco JanesAndrea BernardiniBirgit HöglAmbra StefaniAbubaker IbrahimKarel SonkaDavid KemlinkWolfgang OertelAnnette JanzenGiuseppe PlazziFrancesco BiscariniElena AntelmiMichela FigorilliMonica PulighedduBrit MollenhauerClaudia TrenkwalderFriederike Sixel-DöringValérie Cochen De CockChristelle Charley MonacaAnna HeidbrederLuigi Ferini-StrambiFemke DijkstraMineke ViaeneBeatriz AbrilBradley F Boevenull nullSonja W ScholzMina RytenSara Bandres-CigaAlastair J NoycePaul CannonLasse PihlstrømMike A NallsAndrew B SingletonGuy A RouleauRonald B PostumaZiv Gan OrPublished in: Nature communications (2022)
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.
Keyphrases
- genome wide association study
- genome wide
- poor prognosis
- sleep quality
- physical activity
- randomized controlled trial
- white matter
- resting state
- binding protein
- dna methylation
- functional connectivity
- copy number
- depressive symptoms
- current status
- multiple sclerosis
- long non coding rna
- cerebral ischemia
- subarachnoid hemorrhage
- brain injury