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The SOD1-mediated ALS phenotype shows a decoupling between age of symptom onset and disease duration

Author

Listed:
  • Sarah Opie-Martin

    (Psychology and Neuroscience, King’s College London)

  • Alfredo Iacoangeli

    (Psychology and Neuroscience, King’s College London
    Institute of Psychiatry Psychology & Neuroscience, King’s College London
    NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London)

  • Simon D. Topp

    (Psychology and Neuroscience, King’s College London)

  • Olubunmi Abel

    (Homerton University Hospital)

  • Keith Mayl

    (Psychology and Neuroscience, King’s College London)

  • Puja R. Mehta

    (Psychology and Neuroscience, King’s College London)

  • Aleksey Shatunov

    (Psychology and Neuroscience, King’s College London
    University of Liverpool
    Institute of Medicine, North-Eastern Federal University)

  • Isabella Fogh

    (Psychology and Neuroscience, King’s College London)

  • Harry Bowles

    (Psychology and Neuroscience, King’s College London)

  • Naomi Limbachiya

    (Psychology and Neuroscience, King’s College London)

  • Thomas P. Spargo

    (Psychology and Neuroscience, King’s College London)

  • Ahmad Al-Khleifat

    (Psychology and Neuroscience, King’s College London)

  • Kelly L. Williams

    (Macquarie University)

  • Jennifer Jockel-Balsarotti

    (Washington University School of Medicine)

  • Taha Bali

    (Washington University School of Medicine)

  • Wade Self

    (Washington University School of Medicine)

  • Lyndal Henden

    (Macquarie University)

  • Garth A. Nicholson

    (Macquarie University
    Concord Repatriation Hospital)

  • Nicola Ticozzi

    (IRCCS Istituto Auxologico Italiano
    Università degli Studi di Milano)

  • Diane McKenna-Yasek

    (University of Massachusetts Medical School)

  • Lu Tang

    (Peking University Third Hospital)

  • Pamela J. Shaw

    (University of Sheffield)

  • Adriano Chio

    (University of Turin
    AOU Città della Salute e della Scienza of Torino)

  • Albert Ludolph

    (Ulm University
    DZNE)

  • Jochen H. Weishaupt

    (University of Ulm
    Heidelberg University)

  • John E. Landers

    (University of Massachusetts Medical School)

  • Jonathan D. Glass

    (Emory University School of Medicine)

  • Jesus S. Mora

    (Hospital San Rafael)

  • Wim Robberecht

    (Univeristy Hospitals Leuven)

  • Philip Van Damme

    (Univeristy Hospitals Leuven
    KU Leuven and Center for Brain & Disease Research VIB Leuven)

  • Russell McLaughlin

    (Trinity College Dublin)

  • Orla Hardiman

    (Trinity Biomedical Sciences Institute, Trinity College Dublin)

  • Leonard Berg

    (University Medical Center Utrecht)

  • Jan H. Veldink

    (University Medical Center Utrecht)

  • Phillippe Corcia

    (Centre de Référence pour la SLA et les Autres Maladies du Motoneurone (FILSLAN)
    Centre de Compétences Neuropathies Amyloïdes Familiales et Autres Neuropathies Périphériques Rares (NNERF))

  • Zorica Stevic

    (University of Belgrade)

  • Nailah Siddique

    (Feinberg School of Medicine)

  • Vincenzo Silani

    (IRCCS Istituto Auxologico Italiano
    Università degli Studi di Milano)

  • Ian P. Blair

    (Macquarie University)

  • Dong-sheng Fan

    (Peking University Third Hospital)

  • Florence Esselin

    (University Hospital Gui de Chauliac)

  • Elisa Cruz

    (University Hospital Gui de Chauliac)

  • William Camu

    (University Hospital Gui de Chauliac)

  • Nazli A. Basak

    (School of Medicine Translational Medicine Research Center KUTTAM-NDAL)

  • Teepu Siddique

    (Feinberg School of Medicine)

  • Timothy Miller

    (Washington University School of Medicine)

  • Robert H. Brown

    (University of Massachusetts Medical School)

  • Ammar Al-Chalabi

    (Psychology and Neuroscience, King’s College London)

  • Christopher E. Shaw

    (School of Neuroscience, King’s College London
    University of Auckland)

Abstract

Superoxide dismutase (SOD1) gene variants may cause amyotrophic lateral sclerosis, some of which are associated with a distinct phenotype. Most studies assess limited variants or sample sizes. In this international, retrospective observational study, we compare phenotypic and demographic characteristics between people with SOD1-ALS and people with ALS and no recorded SOD1 variant. We investigate which variants are associated with age at symptom onset and time from onset to death or censoring using Cox proportional-hazards regression. The SOD1-ALS dataset reports age of onset for 1122 and disease duration for 883 people; the comparator population includes 10,214 and 9010 people respectively. Eight variants are associated with younger age of onset and distinct survival trajectories; a further eight associated with younger onset only and one with distinct survival only. Here we show that onset and survival are decoupled in SOD1-ALS. Future research should characterise rarer variants and molecular mechanisms causing the observed variability.

Suggested Citation

  • Sarah Opie-Martin & Alfredo Iacoangeli & Simon D. Topp & Olubunmi Abel & Keith Mayl & Puja R. Mehta & Aleksey Shatunov & Isabella Fogh & Harry Bowles & Naomi Limbachiya & Thomas P. Spargo & Ahmad Al-K, 2022. "The SOD1-mediated ALS phenotype shows a decoupling between age of symptom onset and disease duration," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34620-y
    DOI: 10.1038/s41467-022-34620-y
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