Investigating the genetic background of rapid eye movement (REM)-sleep behaviour disorder to predict alpha-synucleinopathies
Description: Parkinson's disease, dementia with Lewy bodies, and multiple systems atrophy are collectively known as αlpha-synucleinopathies, which are characterized by aggregation and accumulation of αlpha-synuclein. Neurodegeneration at the time of diagnosis is irreversible, resulting in poor prognosis and failed outcomes in clinical trials. The majority individuals with rapid-eye-movement (REM)-sleep behaviour disorder (RBD) later develop alpha-synucleinopathies, providing potential for an earlier diagnosis. Advances in genomic approaches such as high-throughput sequencing have grown rapidly over the last few decades, and allow for a cost-effective and comprehensive investigation of the underlying genetic background in disease phenotypes. This research proposal offers the use of these tools to investigate the genetic background of RBD and its overlap with the genetic backgrounds of αlpha-synucleinopathies. Gene-based burden analyses will be conducted on whole genome sequencing (WGS) data from patients and controls to investigate the accumulation of rare variants in one of the cohorts compared to the others. Genes with the most accumulation of variants will then be sequenced in additional RBD samples and controls. Copy number variant analyses on WGS data cohorts will be performed, followed by association and regression tests to assess whether the variants are associated with increased or reduced risks of developing RBD and the three αlpha-synucleinopathies. The identification of candidate genes and their variants in RBD and αlpha-synucleinopathies will facilitate understanding of the mechanisms and genetic background underlying these neurodegenerative diseases, potentially allowing for earlier diagnoses and improved clinical trial outcomes for neuroprotective therapies.
Amount: CA$17,500
Funding type: fellowship
Funder scheme: Master's Award: Canada Graduate Scholarships
Start date: 2021-09-01
End date: 2022-08-31
Investigator: Shahrzad Rahmanian
Institution: University of Toronto
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Funded outputs count: 0
Funder award ID: 177091_1
OpenAlex ID: G7673011374