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@ARTICLE{OpieMartin:165577,
author = {Opie-Martin, Sarah and Iacoangeli, Alfredo and Topp, Simon
D and Abel, Olubunmi and Mayl, Keith and Mehta, Puja R and
Shatunov, Aleksey and Fogh, Isabella and Bowles, Harry and
Limbachiya, Naomi and Spargo, Thomas P and Al-Khleifat,
Ahmad and Williams, Kelly L and Jockel-Balsarotti, Jennifer
and Bali, Taha and Self, Wade and Henden, Lyndal and
Nicholson, Garth A and Ticozzi, Nicola and McKenna-Yasek,
Diane and Tang, Lu and Shaw, Pamela J and Chio, Adriano and
Ludolph, Albert and Weishaupt, Jochen H and Landers, John E
and Glass, Jonathan D and Mora, Jesus S and Robberecht, Wim
and Damme, Philip Van and McLaughlin, Russell and Hardiman,
Orla and van den Berg, Leonard and Veldink, Jan H and
Corcia, Phillippe and Stevic, Zorica and Siddique, Nailah
and Silani, Vincenzo and Blair, Ian P and Fan, Dong-Sheng
and Esselin, Florence and de la Cruz, Elisa and Camu,
William and Basak, Nazli A and Siddique, Teepu and Miller,
Timothy and Brown, Robert H and Al-Chalabi, Ammar and Shaw,
Christopher E},
title = {{T}he {SOD}1-mediated {ALS} phenotype shows a decoupling
between age of symptom onset and disease duration.},
journal = {Nature Communications},
volume = {13},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DZNE-2022-01717},
pages = {6901},
year = {2022},
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.},
keywords = {Humans / Superoxide Dismutase-1: genetics / Amyotrophic
Lateral Sclerosis: genetics / Amyotrophic Lateral Sclerosis:
epidemiology / Superoxide Dismutase: genetics / Phenotype /
Mutation / Superoxide Dismutase-1 (NLM Chemicals) /
Superoxide Dismutase (NLM Chemicals) / SOD1 protein, human
(NLM Chemicals)},
cin = {Clinical Study Center Ulm},
ddc = {500},
cid = {I:(DE-2719)5000077},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36371497},
pmc = {pmc:PMC9653399},
doi = {10.1038/s41467-022-34620-y},
url = {https://pub.dzne.de/record/165577},
}