Overview
Description
Progressive supranuclear palsy (PSP) is a rare Parkinsonian disorder characterized by problems with movement, balance, cognition, and other symptoms. PSP differs from Alzheimer’s disease (AD) and other neurodegenerative diseases displaying abnormal forms of the microtubule-associated protein tau (“tauopathies”) by the presence of pathology not only in neurons, but also in astrocytes and oligodendrocytes. Genetic contributors may mediate these differences, however much of PSP genetics remains unexplained. Here we conducted the largest genome-wide association study (GWAS) of PSP to date including 2,779 cases (2,595 neuropathologically-confirmed) and 5,584 controls and identified six independent PSP susceptibility loci with genome-wide significant (p < 5×10-8) associations including five known (MAPT, MOBP, STX6, RUNX2, SLCO1A2) and one novel locus (C4A).
Principal Investigators
- Adam Naj — University of Pennsylvania
- Gerard Schellenberg — University of Pennsylvania
- John Crary — Icahn School of Medicine
Funding Sources
R01 AG054008, R01 NS095252, R01 AG060961, R01 NS086736, R01 AG062348 P30 AG066514, K01 AG070326, P01 AG017586, U54 NS100693, UG3 NS104095; RF1 AG074328-01, P30 AG072979, U01 AG032984, RC2 AG036528, U24 AG021886, U24-AG041689, R01 AG054060, RF1 AG061351, R56-AG055824, U01-AG068880 U54-NS123743, NS123746, K08AG065519, 3UH3NS104095, U54 NS100693, P50 AG016574
Publications
- Höglinger GU. Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. Nature genetics. 2011 Jun 19. PubMed link
- Sanchez-Contreras MY. Replication of progressive supranuclear palsy genome-wide association study identifies SLCO1A2 and DUSP10 as new susceptibility loci. Molecular neurodegeneration. 2018 Jul 9. PubMed link
- Chen JA. Joint genome-wide association study of progressive supranuclear palsy identifies novel susceptibility loci and genetic correlation to neurodegenerative diseases. Molecular neurodegeneration. 2018 Aug 8. PubMed link
- Farrell K. Genetic, transcriptomic, histological, and biochemical analysis of progressive supranuclear palsy implicates glial activation and novel risk genes. Nature communications. 2024 Sep 9. PubMed link