medRxivGenetic & Genomic MedicinePreprint
Genome-wide association study of REM sleep behavior disorder identifies novel loci with distinct polygenic and brain expression effects
Lynne KrohniD, Karl HeilbroniD, Cornelis BlauwendraatiD, Regina Hertfelder ReynoldsiD, Eric YuiD, Konstantin A. SenkevichiD, Uladzislau RudakouiD, Mehrdad A. EstiariD, Emil Karl GustavssoniD, Kajsa Atterling BroliniD, Jennifer A. RuskeyiD, Kathryn Freeman, Farnaz AsayeshiD, Ruth ChiaiD, Isabelle ArnulfiD, Michele T.M. HuiD, Jacques Yves MontplaisiriD, Jean‐François GagnoniD, Alex DésautelsiD, Yves A DauvilliersiD, Gian Luigi GigliiD, Mariarosaria ValenteiD, Francesco JanesiD, Andrea BernardiniiD, Birgit HögliD, , Ziv Gan‐OriD
Abstract
Rapid eye movement (REM) sleep behavior disorder (RBD), enactment of dreams during REM sleep, is an early clinical symptom of alpha-synucleinopathies. RBD also defines more severe forms of alpha-synucleinopathies. The genetic background of RBD and its underlying mechanisms are not well understood. Here, we performed the first genome-wide association study of RBD, identifying five RBD risk loci. Expression analyses highlight SNCA-AS1 and SCARB2 differential expression in different brain regions in RBD, with SNCA-AS1 further supported by colocalization analyses. Genetic risk score and other analyses provide further insights into RBD genetics, highlighting RBD as a unique subpopulation that will allow future early intervention.
- organism: human
- assay: GWAS summary statistics
- research focus: GWAS / association mapping
- approach: statistical model
- Citations
- 8
Reproducibility ledger
Nobody has reported trying to reproduce this paper yet. Did you replicate an experiment or run the code? Your report saves the next lab a week.
Sign in to file a reproducibility report.
Related papers
- Genome-wide association study of REM sleep behavior disorder in Parkinson's disease
Yuri Ludwig Sosero, Karl Heilbron, … Ziv Gan‐Or·npj Parkinson s DiseasePeer-reviewed·Sep 25, 2025
- Fine-mapping of SNCA in REM sleep behavior disorder and overt synucleinopathies
Lynne Krohn, Richard Y. J. Wu, … Ziv Gan‐Or·Annals of NeurologyPeer-reviewed·Jan 24, 2020
- Dispersed Sleep Microstates and Associated Structural Changes in GBA1 Mouse: Relevance to Rapid Eye Movement Behavior Disorder
Çiğdem Gelegen, Diana Cash, … Ivana Rosenzweig·bioRxiv·May 26, 2021
- The non-coding GBA1 rs3115534 variant is associated with REM sleep behavior disorder in Nigerians
Oluwadamilola Omolara Ojo, Sara Bandrés‐Ciga, … Njideka Ulunma Okubadejo·Movement DisordersPeer-reviewed·Feb 23, 2024
- Cell vulnerability within the sublaterodorsal tegmental nucleus underlies REM sleep behaviour disorder in prodromal α-synucleinopathy
Russell Luke, Han Soo Yoo, … Kelvin C. Luk·bioRxiv·May 1, 2026
- Altered Brain Dynamics in idiopathic REM sleep behavior disorder: Implications for a continuum from prodromal to overt alpha-synucleinopathies
M. Roascio, S. H. Wang, … G. Arnulfo·bioRxiv·May 5, 2023