Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways

Academic Article


  • 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.
  • Published In

  • Science  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 7494329
  • Author List

  • Cirulli ET; Lasseigne BN; Petrovski S; Sapp PC; Dion PA; Leblond CS; Couthouis J; Lu YF; Wang Q; Krueger BJ
  • Start Page

  • 1436
  • End Page

  • 1441
  • Volume

  • 347
  • Issue

  • 6229