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

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Opie-Martin, Sarah, Iacoangeli, Alfredo, Topp, Simon D, Abel, Olubunmi, Mayl, Keith, Mehta, Puja R, Shatunov, Aleksey ORCID: 0000-0002-2671-8040, Fogh, Isabella, Bowles, Harry, Limbachiya, Naomi et al (show 39 more authors) , Spargo, Thomas P, Al-Khleifat, Ahmad, Williams, Kelly L, Jockel-Balsarotti, Jennifer, Bali, Taha, Self, Wade, Henden, Lyndal, Nicholson, Garth A, Ticozzi, Nicola, McKenna-Yasek, Diane, Tang, Lu, Shaw, Pamela J, Chio, Adriano, Ludolph, Albert, Weishaupt, Jochen H, Landers, John E, Glass, Jonathan D, Mora, Jesus S, Robberecht, Wim, Van Damme, Philip, McLaughlin, Russell, Hardiman, Orla, van den Berg, Leonard, Veldink, Jan H, Corcia, Phillippe, Stevic, Zorica, Siddique, Nailah, Silani, Vincenzo, Blair, Ian P, Fan, Dong-sheng, Esselin, Florence, de la Cruz, Elisa, Camu, William, Basak, Nazli A, Siddique, Teepu, Miller, Timothy, Brown, Robert H, Al-Chalabi, Ammar and Shaw, Christopher E (2022) The <i>SOD1</i>-mediated ALS phenotype shows a decoupling between age of symptom onset and disease duration. NATURE COMMUNICATIONS, 13 (1). 6901-.

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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.

Item Type:	Article
Uncontrolled Keywords:	Humans, Amyotrophic Lateral Sclerosis, Superoxide Dismutase, Phenotype, Mutation, Superoxide Dismutase-1
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	28 Mar 2023 15:33
Last Modified:	18 Oct 2023 01:10
DOI:	10.1038/s41467-022-34620-y
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3169335