Functional validation of a mitochondria-specific polygenic risk score in patient-based models for stratification of idiopathic Parkinson's disease

Background: A large body of evidence specifically points to mitochondrial dysfunction as a major cause of Parkinson’s disease (PD) pathogenesis. Given that only ~10% of PD cases can be attributed to monogenic causes, we hypothesize that a fraction of
idiopathic PD (iPD) cases may harbour a pathogenic combination of common variants in mitochondrial genes ultimately resulting in mitochondrial dysfunction.
Objectives: To gain essential knowledge on the contribution of genetic variability in nuclear-encoded mitochondrial genes to iPD pathogenesis. Starting from genomic data, we aim to functionally validate mitochondrial polygenic risk profiles in patient-based
cellular models, thus defining mitochondrial pathways potentially involved in neurodegeneration in subgroups of iPD patients.