Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9NU, UK.
Department of Biostatistics and Health Informatics, Institute of Psychiatry Psychology & Neuroscience, King's College London, SE5 8AF, London, UK.
Nat Commun. 2022 Nov 12;13(1):6901. doi: 10.1038/s41467-022-34620-y.
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.
超氧化物歧化酶 1(SOD1)基因变异可能导致肌萎缩侧索硬化症,其中一些与特定的表型有关。大多数研究评估的都是有限的变异或样本量。在这项国际性的回顾性观察研究中,我们比较了 SOD1-ALS 患者与无记录的 SOD1 变异的 ALS 患者之间的表型和人口统计学特征。我们使用 Cox 比例风险回归来研究哪些变异与症状发作时的年龄以及从发病到死亡或删失的时间有关。SOD1-ALS 数据集报告了 1122 名患者的发病年龄和 883 名患者的疾病持续时间;对照组分别包括 10214 名和 9010 名患者。有 8 个变异与发病年龄较小和不同的生存轨迹有关;还有 8 个变异仅与发病年龄较小有关,1 个变异仅与生存情况不同有关。在这里,我们表明 SOD1-ALS 中的发病和生存是分离的。未来的研究应该描述导致这种可观察到的变异性的罕见变异和分子机制。