@article{d811de91cb40479887122cb55911e087,
title = "The SOD1-mediated ALS phenotype shows a decoupling between age of symptom onset and disease duration",
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.",
author = "Sarah Opie-Martin and Alfredo Iacoangeli and Topp, {Simon D.} and Olubunmi Abel and Keith Mayl and Mehta, {Puja R.} and Aleksey Shatunov and Isabella Fogh and Harry Bowles and Naomi Limbachiya and Spargo, {Thomas P.} and Ahmad Al-Khleifat and Williams, {Kelly L.} and Jennifer Jockel-Balsarotti and Taha Bali and Wade Self and Lyndal Henden and Nicholson, {Garth A.} and Nicola Ticozzi and Diane McKenna-Yasek and Lu Tang and Shaw, {Pamela J.} and Adriano Chio and Albert Ludolph and Weishaupt, {Jochen H.} and Landers, {John E.} and Glass, {Jonathan D.} and Mora, {Jesus S.} and Wim Robberecht and Damme, {Philip Van} and Russell McLaughlin and Orla Hardiman and {van den Berg}, Leonard and Veldink, {Jan H.} and Phillippe Corcia and Zorica Stevic and Nailah Siddique and Vincenzo Silani and Blair, {Ian P.} and Fan, {Dong sheng} and Florence Esselin and {de la Cruz}, Elisa and William Camu and Basak, {Nazli A.} and Teepu Siddique and Timothy Miller and Brown, {Robert H.} and Ammar Al-Chalabi and Shaw, {Christopher E.}",
note = "Funding Information: The project is supported through the following funding organisations under the egis of JPND— https://www.neurodegenerationresearch.eu (United Kingdom, Medical Research Council [MR/L501529/1] and Economic and Social Research Council [ES/ L008238/1]) (Author: A.A.C.). The work leading up to this publication was funded by the European Community{\textquoteright}s Health Seventh Framework Programme [FP7/2007–2013; grant agreement number 259867], Horizon 2020 Framework Programme [H2020-PHC-2014-two-stage; grant agreement number 633413] and Programme Grants for Applied Research (Author A.A.C.). This project is also supported by funding from Avexis/Novartis, the United Kingdom Dementia Research Institute and the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre at South London Maudsley Foundation Trust and King{\textquoteright}s College London (Authors A.A.C./C.E.S.). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. We have also received funding from the Motor Neurone Disease Association, ALS Association, Patients Like Me and the Psychiatry Research Trust (Authors AAC/CES/AI/SOM). This project has received funding from the European Research Council (ERC) under the European Union{\textquoteright}s Horizon 2020 research and innovation programme (grant agreement n° 772376 – EScORIAL (Author A.A.C.). The collaboration project is co-funded by the PPP Allowance made available by Health~Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships. This study was supported by the ALS Foundation Netherlands (Authors: J.H.V./L.B.). Funding Information: J.H.V. reports to have sponsored research agreements with Biogen. P.V.D. holds a senior clinical investigatorship of FWO-Vlaanderen and is supported by the E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders, the ALS Liga Belgi{\"e} and the KU Leuven funds “Een Hart voor ALS”, “Laeversfonds voor ALS Onderzoek” and the “Val{\'e}ry Perrier Race against ALS Fund”. Several authors of this publication (A.C., A.L., J.W., L.B., O.H., V.S.) are members of the European Reference Network for Rare Neuromuscular Diseases (ERN-NMD). The remaining authors declare no conflicts of interest. Funding Information: The project is supported through the following funding organisations under the egis of JPND—https://www.neurodegenerationresearch.eu (United Kingdom, Medical Research Council [MR/L501529/1] and Economic and Social Research Council [ES/ L008238/1]) (Author: A.A.C.). The work leading up to this publication was funded by the European Community{\textquoteright}s Health Seventh Framework Programme [FP7/2007–2013; grant agreement number 259867], Horizon 2020 Framework Programme [H2020-PHC-2014-two-stage; grant agreement number 633413] and Programme Grants for Applied Research (Author A.A.C.). This project is also supported by funding from Avexis/Novartis, the United Kingdom Dementia Research Institute and the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre at South London Maudsley Foundation Trust and King{\textquoteright}s College London (Authors A.A.C./C.E.S.). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. We have also received funding from the Motor Neurone Disease Association, ALS Association, Patients Like Me and the Psychiatry Research Trust (Authors AAC/CES/AI/SOM). This project has received funding from the European Research Council (ERC) under the European Union{\textquoteright}s Horizon 2020 research and innovation programme (grant agreement n° 772376 – EScORIAL (Author A.A.C.). The collaboration project is co-funded by the PPP Allowance made available by Health~Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships. This study was supported by the ALS Foundation Netherlands (Authors: J.H.V./L.B.). Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41467-022-34620-y",
language = "English",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}