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Updated: Sep 6, 2025
Real-Time Fluorescent Measurement of Synaptic Functions in Models of Amyotrophic Lateral Sclerosis
Published on: July 16, 2021
Genetic factors for survival in amyotrophic lateral sclerosis: an integrated approach combining a systematic review,
Wei-Ming Su1,2,3, Xiao-Jing Gu1,2,3, Qing-Qing Duan1,2,3
1Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
Background:
The time of survival in patients with amyotrophic lateral sclerosis (ALS) varies greatly, and the genetic factors that contribute to the survival of ALS are not well studied. There is a lack of a comprehensive study to elucidate the role of genetic factors in the survival of ALS.
Methods:
The published studies were systematically searched and obtained from PubMed, EMBASE, and the Cochrane Library without any language restrictions from inception to Oct 27, 2021. A network meta-analysis for ALS causative/risk genes and a systematic review and pairwise meta-analysis for other genetic modifiers were conducted. The PROSPERO registration number: CRD42022311646.
Results:
A total of 29,764 potentially relevant references were identified, and 71 papers were eligible for analysis based on pre-decided criteria, including 35 articles in network meta-analysis for 9 ALS causative/risk genes, 17 articles in pairwise meta-analysis for four genetic modifiers, and 19 articles described in the systematic review. Variants in three genes, including ATXN2 (HR: 3.6), C9orf72 (HR: 1.6), and FUS (HR:1.8), were associated with short survival of ALS, but such association was not identified in SOD1, TARDBP, TBK1, NEK1, UBQLN2, and CCNF. In addition, UNC13A rs12608932 CC genotype and ZNF521B rs2275294 C allele also caused a shorter survival of ALS; however, APOE ε4 allele and KIFAP3 rs1541160 did not be found to have any effect on the survival of ALS.
Conclusions:
Our study summarized and contrasted evidence for prognostic genetic factors in ALS and would help to understand ALS pathogenesis and guide clinical trials and drug development.
