https://scholars.lib.ntu.edu.tw/handle/123456789/431807
標題: | Burden of rare variants in ALS genes influences survival in familial and sporadic ALS | 作者: | Pang, SYY Jacob Shujui Hsu Teo, KC Li, Y Kung, MHW Cheah, KSE Chan, D Cheung, KMC Li, MX Sham, PC Ho, SL |
關鍵字: | ALS; Genetics; Next generation sequencing; Survival | 公開日期: | 2017 | 出版社: | ELSEVIER SCIENCE INC | 卷: | 58 | 來源出版物: | Neurobiology of Aging | 摘要: | Genetic variants are implicated in the development of amyotrophic lateral sclerosis (ALS), but it is unclear whether the burden of rare variants in ALS genes has an effect on survival. We performed whole genome sequencing on 8 familial ALS (FALS) patients with superoxide dismutase 1 (SOD1) mutation and whole exome sequencing on 46 sporadic ALS (SALS) patients living in Hong Kong and found that 67% had at least 1 rare variant in the exons of 40 ALS genes; 22% had 2 or more. Patients with 2 or more rare variants had lower probability of survival than patients with 0 or 1 variant (p = 0.001). After adjusting for other factors, each additional rare variant increased the risk of respiratory failure or death by 60% (p = 0.0098). The presence of the rare variant was associated with the risk of ALS (Odds ratio 1.91, 95% confidence interval 1.03-3.61, p = 0.03), and ALS patients had higher rare variant burden than controls (MB, p = 0.004). Our findings support an oligogenic basis with the burden of rare variants affecting the development and survival of ALS. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/431807 | ISSN: | 0197-4580 | DOI: | 10.1016/j.neurobiolaging.2017.06.007 |
顯示於: | 基因體暨蛋白體醫學研究所 |
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