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Genetic, transcriptomic, histological, and biochemical analysis of progressive supranuclear palsy implicates glial activation and novel risk genes

Author

Listed:
  • Kurt Farrell

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Jack Humphrey

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Timothy Chang

    (University of Pennsylvania)

  • Yi Zhao

    (University of Pennsylvania
    University of Pennsylvania)

  • Yuk Yee Leung

    (University of Pennsylvania
    University of Pennsylvania
    University of Pennsylvania)

  • Pavel P. Kuksa

    (University of Pennsylvania
    University of Pennsylvania
    University of Pennsylvania)

  • Vishakha Patil

    (University of Pennsylvania)

  • Wan-Ping Lee

    (University of Pennsylvania
    University of Pennsylvania
    University of Pennsylvania)

  • Amanda B. Kuzma

    (University of Pennsylvania
    University of Pennsylvania)

  • Otto Valladares

    (University of Pennsylvania
    University of Pennsylvania)

  • Laura B. Cantwell

    (University of Pennsylvania
    University of Pennsylvania)

  • Hui Wang

    (University of Pennsylvania
    University of Pennsylvania
    University of Pennsylvania)

  • Ashvin Ravi

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Claudia Sanctis

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Natalia Han

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Thomas D. Christie

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Robina Afzal

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Shrishtee Kandoi

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Kristen Whitney

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Margaret M. Krassner

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Hadley Ressler

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • SoongHo Kim

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Diana Dangoor

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Megan A. Iida

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Alicia Casella

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Ruth H. Walker

    (University of California
    University of California)

  • Melissa J. Nirenberg

    (University of California
    University of California)

  • Alan E. Renton

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Bergan Babrowicz

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Giovanni Coppola

    (University of Pennsylvania)

  • Towfique Raj

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Günter U. Höglinger

    (University of California
    James J. Peters Veterans Affairs Medical Center
    Icahn School of Medicine at Mount Sinai)

  • Ulrich Müller

    (Ludwig-Maximilians-Universität Hospital)

  • Lawrence I. Golbe

    (Munich Cluster for Systems Neurology (SyNergy)
    German Center for Neurodegenerative Diseases (DZNE))

  • Huw R. Morris

    (Justus-Liebig University
    Rutgers Robert Wood Johnson Medical School)

  • John Hardy

    (Rutgers Robert Wood Johnson Medical School
    Inc.)

  • Tamas Revesz

    (Rutgers Robert Wood Johnson Medical School
    University College London)

  • Tom T. Warner

    (Justus-Liebig University
    Rutgers Robert Wood Johnson Medical School
    University College London)

  • Zane Jaunmuktane

    (Justus-Liebig University
    Rutgers Robert Wood Johnson Medical School
    University College London)

  • Kin Y. Mok

    (Rutgers Robert Wood Johnson Medical School
    Inc.)

  • Rosa Rademakers

    (University College London
    University College London
    University College London)

  • Dennis W. Dickson

    (University College London)

  • Owen A. Ross

    (University College London)

  • Li-San Wang

    (University of Pennsylvania
    University of Pennsylvania
    University of Pennsylvania)

  • Alison Goate

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Gerard Schellenberg

    (University of Pennsylvania
    University of Pennsylvania)

  • Daniel H. Geschwind

    (University of Pennsylvania
    University of Antwerp
    University of Antwerp
    Mayo Clinic)

  • John F. Crary

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Adam Naj

    (University of Pennsylvania
    University of Pennsylvania
    University of California)

Abstract

Progressive supranuclear palsy (PSP), a rare Parkinsonian disorder, is characterized by problems with movement, balance, and cognition. PSP differs from Alzheimer’s disease (AD) and other diseases, displaying abnormal microtubule-associated protein tau by both neuronal and glial cell pathologies. Genetic contributors may mediate these differences; however, the genetics of PSP remain underexplored. Here we conduct the largest genome-wide association study (GWAS) of PSP which includes 2779 cases (2595 neuropathologically-confirmed) and 5584 controls and identify six independent PSP susceptibility loci with genome-wide significant (P

Suggested Citation

  • Kurt Farrell & Jack Humphrey & Timothy Chang & Yi Zhao & Yuk Yee Leung & Pavel P. Kuksa & Vishakha Patil & Wan-Ping Lee & Amanda B. Kuzma & Otto Valladares & Laura B. Cantwell & Hui Wang & Ashvin Ravi, 2024. "Genetic, transcriptomic, histological, and biochemical analysis of progressive supranuclear palsy implicates glial activation and novel risk genes," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52025-x
    DOI: 10.1038/s41467-024-52025-x
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    References listed on IDEAS

    as
    1. Claudia Giambartolomei & Damjan Vukcevic & Eric E Schadt & Lude Franke & Aroon D Hingorani & Chris Wallace & Vincent Plagnol, 2014. "Bayesian Test for Colocalisation between Pairs of Genetic Association Studies Using Summary Statistics," PLOS Genetics, Public Library of Science, vol. 10(5), pages 1-15, May.
    2. Aswin Sekar & Allison R. Bialas & Heather de Rivera & Avery Davis & Timothy R. Hammond & Nolan Kamitaki & Katherine Tooley & Jessy Presumey & Matthew Baum & Vanessa Van Doren & Giulio Genovese & Samue, 2016. "Schizophrenia risk from complex variation of complement component 4," Nature, Nature, vol. 530(7589), pages 177-183, February.
    3. Daniel Taliun & Daniel N. Harris & Michael D. Kessler & Jedidiah Carlson & Zachary A. Szpiech & Raul Torres & Sarah A. Gagliano Taliun & André Corvelo & Stephanie M. Gogarten & Hyun Min Kang & Achille, 2021. "Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program," Nature, Nature, vol. 590(7845), pages 290-299, February.
    4. Anna-Leigh Brown & Oscar G. Wilkins & Matthew J. Keuss & Sarah E. Hill & Matteo Zanovello & Weaverly Colleen Lee & Alexander Bampton & Flora C. Y. Lee & Laura Masino & Yue A. Qi & Sam Bryce-Smith & Ar, 2022. "TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A," Nature, Nature, vol. 603(7899), pages 131-137, March.
    5. Naomi Kouri & Owen A. Ross & Beth Dombroski & Curtis S. Younkin & Daniel J. Serie & Alexandra Soto-Ortolaza & Matthew Baker & Ni Cole A. Finch & Hyejin Yoon & Jungsu Kim & Shinsuke Fujioka & Catriona , 2015. "Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy," Nature Communications, Nature, vol. 6(1), pages 1-7, November.
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