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

Nat Commun. 2022 Dec 5;13(1):7496. doi: 10.1038/s41467-022-34732-5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain
  • Genome-Wide Association Study
  • Humans
  • Parkinson Disease* / genetics
  • REM Sleep Behavior Disorder* / genetics
  • Synucleinopathies*