TY  - JOUR
AU  - Opie-Martin, Sarah
AU  - Iacoangeli, Alfredo
AU  - Topp, Simon D
AU  - Abel, Olubunmi
AU  - Mayl, Keith
AU  - Mehta, Puja R
AU  - Shatunov, Aleksey
AU  - Fogh, Isabella
AU  - Bowles, Harry
AU  - Limbachiya, Naomi
AU  - Spargo, Thomas P
AU  - Al-Khleifat, Ahmad
AU  - Williams, Kelly L
AU  - Jockel-Balsarotti, Jennifer
AU  - Bali, Taha
AU  - Self, Wade
AU  - Henden, Lyndal
AU  - Nicholson, Garth A
AU  - Ticozzi, Nicola
AU  - McKenna-Yasek, Diane
AU  - Tang, Lu
AU  - Shaw, Pamela J
AU  - Chio, Adriano
AU  - Ludolph, Albert
AU  - Weishaupt, Jochen H
AU  - Landers, John E
AU  - Glass, Jonathan D
AU  - Mora, Jesus S
AU  - Robberecht, Wim
AU  - Damme, Philip Van
AU  - McLaughlin, Russell
AU  - Hardiman, Orla
AU  - van den Berg, Leonard
AU  - Veldink, Jan H
AU  - Corcia, Phillippe
AU  - Stevic, Zorica
AU  - Siddique, Nailah
AU  - Silani, Vincenzo
AU  - Blair, Ian P
AU  - Fan, Dong-Sheng
AU  - Esselin, Florence
AU  - de la Cruz, Elisa
AU  - Camu, William
AU  - Basak, Nazli A
AU  - Siddique, Teepu
AU  - Miller, Timothy
AU  - Brown, Robert H
AU  - Al-Chalabi, Ammar
AU  - Shaw, Christopher E
TI  - The SOD1-mediated ALS phenotype shows a decoupling between age of symptom onset and disease duration.
JO  - Nature Communications
VL  - 13
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DZNE-2022-01717
SP  - 6901
PY  - 2022
AB  - 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.
KW  - Humans
KW  - Superoxide Dismutase-1: genetics
KW  - Amyotrophic Lateral Sclerosis: genetics
KW  - Amyotrophic Lateral Sclerosis: epidemiology
KW  - Superoxide Dismutase: genetics
KW  - Phenotype
KW  - Mutation
KW  - Superoxide Dismutase-1 (NLM Chemicals)
KW  - Superoxide Dismutase (NLM Chemicals)
KW  - SOD1 protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:36371497
C2  - pmc:PMC9653399
DO  - DOI:10.1038/s41467-022-34620-y
UR  - https://pub.dzne.de/record/165577
ER  -