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Description

For a majority of the cases included in the study, inclusion criteria were a neuropathological diagnosis of Progressive Supranuclear Palsy (PSP; n=2,595), with the exception of a small number of cases, both living and deceased, that only had a neurological diagnosis (n=184). PSP subjects with comorbid pathological features of other neurodegenerative disorders were not excluded from the study including AD-like features, Lewy bodies, and TDP-43 as prevalence of these comorbid features. The controls had no clinical evidence of cognitive impairment or a movement disorder (n=5,584) and neuropathologically could only have age-related pathological changes. A full list of the institutions where the material was collected can be found in our full text publication and it should be noted many of the samples included here were contained in previous studies (Höglinger et. al., 2011; Chen et. al, 2018; Sanchez-Contreras et. al., 2018).

PSP cases and controls were genotyped at three different institutions (University of Pennsylvania, Icahn School of Medicine at Mount Sinai, and the University of California Los Angeles) on three genotyping platforms (Illumina Human660W, Illumina OmniExpress 2.5, and Illumina Global Screening Array) in 10 total batches.  The cases and controls were genotyped at each of the respective institutions, merged, and harmonized to contain the same variants and single nucleotide polymorphism (SNP) and sample level quality control was performed followed by imputation. The process was repeated by combining the data from the three centers and the overlapping variants were again harmonized.

PLINK v1.9 was used to perform quality control. SNP exclusion criteria included minor allele frequency < 1%, genotyping call-rate filter less than 95%, and Hardy–Weinberg threshold of 1 × 10−6. Individuals with discordant sex, non-European ancestry, genotyping failure of > 5%, or relatedness of > 0.1 were excluded. A principal component analysis (PCA) was performed to identify population substructure using EIGENSTRAT v6.1.4 and the 1000 genomes reference panel. Samples were excluded if they were six standard deviations away from the European population cluster. Each dataset was imputed on the Trans-Omics for Precision Medicine (TOPMed) Imputation Server (TIS) using the multi-ancestry release 5 (R5) reference panel which includes data on from 97,256 participants with 308,107,085 SNPs observed on 194,512 haplotypes.

Phasing was performed on the TIS using EAGLE with subsequent imputation using Minimac. Imputed variants were filtered using a conservative quality threshold, R 2≥0.8, to assure high quality of variants, and additional filtering on variants overlapping all genotype sets with MAF>0.01 was performed prior to analysis. Single-variant genome-wide association analyses was performed jointly on all imputed datasets using a score-based logistic regression under an additive model with covariate adjustment for sex, the first three PC eigenvectors for population substructure, and indicator variables for genotyping platform to mitigate potential batch effects. All association analyses were performed using the program SNPTEST 63. After analysis, variants with regression coefficient of |β|>5 and any erroneous estimates (negative standard errors or P-values equal to 0 or 1) were excluded from further analysis.

Available Filesets

NameAccessionLatest ReleaseDescription
PSP Summary Statistics - 2024: Full Summary Statistics (application needed)fsa000111NG00169.v1Full Summary Statistics
PSP Summary Statistics - 2024: P-values only (open access)fsa000112NG00169.v1p-values Only

View the File Manifest for a full list of files released in this dataset.

Consent LevelNumber of Subjects
DS-ADRD-IRB-PUB-NPUNA

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Acknowledgment statement for any data distributed by NIAGADS:

Data for this study were prepared, archived, and distributed by the National Institute on Aging Alzheimer’s Disease Data Storage Site (NIAGADS) at the University of Pennsylvania (U24-AG041689), funded by the National Institute on Aging.

Use the study-specific acknowledgement statements below (as applicable):

For investigators using any data from this dataset:

Please cite/reference the use of NIAGADS data by including the accession NG00169.

For investigators using Genetic, transcriptomic, histological, and biochemical analysis of progressive supranuclear palsy implicates glial activation and novel risk genes – Farrell et al., 2024 (sa000054) data:

The authors would like to acknowledge the following tissue repositories for providing the materials necessary to conduct the study: University of Louisville, Australian Brain Bank Network and Flinders University, Barcelona Biobanc and The University of Barcelona, Brain-Net Germany and Neurobiobank Munich, Emory University, Harvard Brain Tissue Resource Center, McLean Brain Bank, Indiana University School of Medicine, Johns Hopkins University, London brain bank, Los Angeles Veterans Association hospital brain bank, Ludwig-Maximilians- Universität München, German Center for Neurodegenerative Diseases (DZNE), Madrid (Universidad Autónoma de Madrid Spain), Massachusetts General Institute for Neurodegenerative Disease, Mayo Clinic Jacksonville, Netherlands Brain Bank and Erasmus University, New York Brain Bank, Columbia University, University of Paris, Southern Texas University, Sun Health Research Institute, University College London Queen Square Institute of NeurologyQueen Square Brain Bank for Neurological Disorders, University of California San Diego, University of California San Francisco Memory and Aging Center, University of Antwerp, University of Michigan, University of Navarra, University of Saskatchewan, University of Southern California, University of Toronto, University of Washington, University of Würzburg, Victorian Brain Bank, Boston University, Emory University, Netherlands Brain Bank and Erasmus University, Oregon Health Sciences University, University of Pittsburgh, University of Miami, University of Washington, University of California Irvine and the NIH Neurobiobank

Crary/Farrell Labs: [R01 AG054008, R01 NS095252, R01 AG060961, R01 NS086736, and R01 AG062348 P30 AG066514 to J.F.C. K01 AG070326 and CurePSP 685-2023-06-Pathway to K.F.], the Rainwater Charitable Foundation / Tau Consortium, Karen Strauss Cook Research Scholar Award, Stuart Katz & Dr. Jane Martin. Penn/Lee/Naj/Wang/Schellenberg Labs: [P01 AG017586, U54 NS100693, and UG3 NS104095; RF1 AG074328-01, and P30 AG072979; CurePSP Consortium; Controls were drawn from the ADGC (U01 AG032984, RC2 AG036528), and included samples from the National Cell Repository for Alzheimer’s Disease (NCRAD), which receives government support under a cooperative agreement grant (U24 AG021886) awarded by the National Institute on Aging (NIA). We thank contributors who collected samples used in this study, as well as patients and their families, whose help and participation made this work possible; Control data for this study were prepared, archived, and distributed by the National Institute on Aging Alzheimer’s Disease Data Storage Site (NIAGADS) at the University of Pennsylvania (U24-AG041689); additional salary and analytical support were provided by NIA grants R01 AG054060 and RF1 AG061351] Raj/Humphrey/Ravi: [R56-AG055824, U01-AG068880 U54-NS123743 to J.H., A.R., and T.R.] Goate Lab: [Rainwater Charitable Foundation, NS123746] UCLA/Geschwind lab: [K08AG065519, 3UH3NS104095, Larry L Hillblom Foundation, Tau Consortium] Ross/Dickson: U54 NS100693, P50 AG016574, CurePSP Foundation, Mayo Foundation Hardy lab: The Dolby Foundation Höglinger Lab: Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198), DFG (HO2402/18-1 MSAomics), the German Federal Ministry of Education and Research (BMBF, 01KU1403A EpiPD; 01EK1605A HitTau); Niedersächsisches Ministerium für Wissenschaft und Kunst / VolkswagenStiftung (Niedersächsisches Vorab), Petermax-Müller Foundation (Etiology and Therapy of Synucleinopathies and Tauopathies)

Farrell K., et al. Genetic, transcriptomic, histological, and biochemical analysis of progressive supranuclear palsy implicates glial activation and novel risk genes. bioRxiv. 2023 Nov. doi: 10.1101/2023.11.09.565552

Höglinger G. U., et al. Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. Nat Genet. 2011 Jun. doi: 10.1038/ng.859 PubMed link

Sanchez-Contreras M. Y., et al. Replication of progressive supranuclear palsy genome-wide association study identifies SLCO1A2 and DUSP10 as new susceptibility loci. Mol Neurodegener. 2018 Jul. 10.1186/s13024-018-0267-3 PubMed link

Chen J. A., et al. Joint genome-wide association study of progressive supranuclear palsy identifies novel susceptibility loci and genetic correlation to neurodegenerative diseases. Mol Neurodegener. 2018 Aug. 10.1186/s13024-018-0270-8 PubMed link