title: Genetic epidemiology of amyotrophic lateral sclerosis: a systematic review and meta-analysis.
abstract: Genetic studies have shown thatC9orf72,SOD1,TARDBPandFUSare the most common mutated genes in amyotrophic lateral sclerosis (ALS). Here, we performed a meta-analysis to determine the mutation frequencies of these major ALS-related genes in patients with ALS.
  
  
  
  We performed an extensive literature research to identify all original articles reporting frequencies ofC9orf72,SOD1,TARDBPandFUSmutations in ALS. The mutation frequency and effect size of each study were combined. Possible sources of heterogeneity across studies were determined by meta-regression, sensitivity analysis and subgroup analysis.
  
  
  
  111 studies were included in the meta-analysis. The overall pooled mutation frequencies of these major ALS-related genes were 47.7% in familial amyotrophic lateral sclerosis (FALS) and 5.2% in sporadic ALS (SALS). A significant difference was identified regarding the frequencies of mutations in major ALS genes between European and Asian patients. In European populations, the most common mutations were theC9orf72repeat expansions (FALS 33.7%, SALS 5.1%), followed bySOD1(FALS 14.8%, SALS 1.2%),TARDBP(FALS 4.2%, SALS 0.8%) andFUSmutations (FALS 2.8%, SALS 0.3%), while in Asian populations the most common mutations wereSOD1mutations (FALS 30.0%, SALS 1.5%), followed byFUS(FALS 6.4%, SALS 0.9%),C9orf72(FALS 2.3%, SALS 0.3%) andTARDBP(FALS 1.5%, SALS 0.2%) mutations.
  
  
  
  These findings demonstrated that the genetic architecture of ALS in Asian populations is distinct from that in European populations, which need to be given appropriate consideration when performing genetic testing of patients with ALS.
authors.affiliation: Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China.
authors.forename: Zhang-Yu
authors.identifier: 0000-0002-8277-1110
authors.initials: ZY
authors.lastname: Zou
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Zhi-Rui
authors.initials: ZR
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China.
authors.forename: Chun-Hui
authors.initials: CH
authors.lastname: Che
authors.affiliation: Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China.
authors.forename: Chang-Yun
authors.initials: CY
authors.lastname: Liu
authors.affiliation: Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China.
authors.forename: Rao-Li
authors.initials: RL
authors.lastname: He
authors.affiliation: Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China.
authors.forename: Hua-Pin
authors.initials: HP
authors.lastname: Huang
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D017720:Molecular Epidemiology; D009154:Mutation / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins