The SOD1-mediated ALS phenotype shows a decoupling between age of symptom onset and disease duration
Opie-Martin, Sarah ; Iacoangeli, Alfredo ; Topp, Simon D ; Abel, Olubunmi ; Mayl, Keith ; Mehta, Puja R ; Shatunov, Aleksey ; Fogh, Isabella ; Bowles, Harry ; Limbachiya, Naomi ... show 10 more
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Iacoangeli, Alfredo
Topp, Simon D
Abel, Olubunmi
Mayl, Keith
Mehta, Puja R
Shatunov, Aleksey
Fogh, Isabella
Bowles, Harry
Limbachiya, Naomi
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
Damme, Philip Van
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
Shaw, Christopher E
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UMass Chan Affiliations
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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.
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Opie-Martin S, Iacoangeli A, Topp SD, Abel O, Mayl K, Mehta PR, Shatunov A, Fogh I, Bowles H, Limbachiya N, Spargo TP, Al-Khleifat A, Williams KL, Jockel-Balsarotti J, Bali T, Self W, Henden L, Nicholson GA, Ticozzi N, McKenna-Yasek D, Tang L, Shaw PJ, Chio A, Ludolph A, Weishaupt JH, Landers JE, Glass JD, Mora JS, Robberecht W, Damme PV, McLaughlin R, Hardiman O, van den Berg L, Veldink JH, Corcia P, Stevic Z, Siddique N, Silani V, Blair IP, Fan DS, Esselin F, de la Cruz E, Camu W, Basak NA, Siddique T, Miller T, Brown RH, Al-Chalabi A, Shaw CE. The SOD1-mediated ALS phenotype shows a decoupling between age of symptom onset and disease duration. Nat Commun. 2022 Nov 12;13(1):6901. doi: 10.1038/s41467-022-34620-y. PMID: 36371497; PMCID: PMC9653399.