Genetic epidemiology of amyotrophic lateral sclerosis: a systematic review and meta-analysis

  title={Genetic epidemiology of amyotrophic lateral sclerosis: a systematic review and meta-analysis},
  author={Zhang-Yu Zou and Zhi-rui Zhou and Chun-Hui Che and Changyun Liu and Raoli He and Huapin Huang},
  journal={Journal of Neurology, Neurosurgery \& Psychiatry},
  pages={540 - 549}
Background Genetic studies have shown that C9orf72, SOD1, TARDBP and FUS are 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. Methods We performed an extensive literature research to identify all original articles reporting frequencies of C9orf72, SOD1, TARDBP and FUS mutations in ALS. The mutation frequency and effect size of each study were… 

Genotype-phenotype correlations in a chinese population with familial amyotrophic lateral sclerosis

The results showed the relative contributions of the different types of mutations associated with ALS and provided phenotype-genotype correlations with clinical features in Chinese patients.

Unique characteristics of the genetics epidemiology of amyotrophic lateral sclerosis in China

The genetic features of ALS in Chinese population are significantly different from those in Caucasian population, indicating an association between genetic susceptibility and origin of population.

Genetic factors for survival in amyotrophic lateral sclerosis: an integrated approach combining a systematic review, pairwise and network meta-analysis

Evidence for prognostic genetic factors in ALS is summarized and contrasted to help to understand ALS pathogenesis and guide clinical trials and drug development.

Genetic Epidemiology of Amyotrophic Lateral Sclerosis in Norway: A 2-Year Population-Based Study

Several pathogenic gene variants in both familial and sporadic ALS patients are identified in a Norwegian population-based cohort, indicating the need for genetic analysis in sporadic cases as well.

Genetic analysis in Chinese patients with familial or young-onset amyotrophic lateral sclerosis

Two novel mutations were detected in patients with familial or young-onset ALS that were predicted to be deleterious, affected evolutionarily highly conserved amino acid residue and the formation of hydrogen bonds between the mutated site and its surrounding amino acid residues.

A natural history comparison of SOD1-mutant patients with amyotrophic lateral sclerosis between Chinese and German populations

The data demonstrate the distinct mutational and clinical spectrums of SOD1-mutant patients in Asian and European populations, and clinical phenotypes seem to be primarily influenced by mutation-specific, albeit not excluding ethnicity-specific factors.

Comprehensive analysis of the mutation spectrum in 301 German ALS families

A comprehensive genetic characterisation of German familial ALS is presented and several previously unreported rare variants are identified and demonstrated the absence of likely pathogenic variants in some of the recently described ALS disease genes.



Large proportion of amyotrophic lateral sclerosis cases in Sardinia due to a single founder mutation of the TARDBP gene.

An extensive screening for mutations of amyotrophic lateral sclerosis (ALS)-related genes in a consecutive cohort of Sardinian patients found that these patients share a large risk haplotype across the TARDBP locus, indicating that they have a common ancestor.

Contribution of major amyotrophic lateral sclerosis genes to the etiology of sporadic disease

A considerable proportion of patients with SALS harbored mutations in major ALS genes, which raises the hypothesis that multiple mutations model may explain genetic architecture of SALS.

The distinctive genetic architecture of ALS in mainland China

An extensive review of the literature was performed to determine the mutation frequencies of major ALS-related genes in mainland China, and the burden of mutations across SOD1, ANG, TARDBP, FUS and C9orf72 within mainland Chinese was compared to that within Caucasian populations.

Classification of familial amyotrophic lateral sclerosis by family history: effects on frequency of genes mutation

Evidence is provided that frequency of mutations in currently known ALS genes varies widely among different FALS categories, and families with only two affected relatives have heterogeneous genetic components, the chance to detect mutations being higher in cases with parent-to-child transmission.

Evidence for an oligogenic basis of amyotrophic lateral sclerosis.

Evidence for an oligogenic aetiology of ALS is provided and may have important implications for the interpretation of whole exome/genome experiments designed to identify new ALS-associated genes and for genetic counselling, especially of unaffected family members.

Prevalence of SOD1 mutations in the Italian ALS population

The frequency of familial amyotrophic lateral sclerosis (FALS) was lower than that reported in series from ALS referral centers, and the frequency of SOD1 mutations in FALS was similar to the data reported in the literature.

Delineating the genetic heterogeneity of ALS using targeted high-throughput sequencing

Background Over 100 genes have been implicated in the aetiology of amyotrophic lateral sclerosis (ALS). A detailed understanding of their independent and cumulative contributions to disease burden

Superoxide dismutase mutations in an unselected cohort of Scottish amyotrophic lateral sclerosis patients.

A study of the prevalence of SOD1 mutations in an unselected cohort of Scottish ALS patients, with both sporadic and familial patients, found one mutation, ile113thr, seems to be particularly prevalent in the Scottish population.