Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways

Research output: Contribution to journalArticleAcademicpeer-review


Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease with no effective treatment. We report the results of a moderate-scale sequencing study aimed at increasing the number of genes known to contribute to predisposition for ALS. We performed whole-exome sequencing of 2869 ALS patients and 6405 controls. Several known ALS genes were found to be associated, and TBK1 (the gene encoding TANK-binding kinase 1) was identified as an ALS gene. TBK1 is known to bind to and phosphorylate a number of proteins involved in innate immunity and autophagy, including optineurin (OPTN) and p62 (SQSTM1/sequestosome), both of which have also been implicated in ALS. These observations reveal a key role of the autophagic pathway in ALS and suggest specific targets for therapeutic intervention.

Original languageEnglish
Pages (from-to)1436-41
Number of pages6
Issue number6229
Publication statusPublished - 27 Mar 2015


  • Adaptor Proteins, Signal Transducing/genetics
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Amyotrophic Lateral Sclerosis/genetics
  • Autophagy/genetics
  • Cell Cycle Proteins
  • Exome/genetics
  • Female
  • Genes
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Membrane Transport Proteins
  • Middle Aged
  • Protein Binding
  • Protein-Serine-Threonine Kinases/genetics
  • Risk
  • Sequence Analysis, DNA
  • Sequestosome-1 Protein
  • Transcription Factor TFIIIA/genetics
  • Young Adult


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