Research Article

Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways

See allHide authors and affiliations

Science  27 Mar 2015:
Vol. 347, Issue 6229, pp. 1436-1441
DOI: 10.1126/science.aaa3650

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

New players in Lou Gehrig's disease

Amyotrophic lateral sclerosis (ALS), often referred to as “Lou Gehrig's disease,” is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Cirulli et al. sequenced the expressed genes of nearly 3000 ALS patients and compared them with those of more than 6000 controls (see the Perspective by Singleton and Traynor). They identified several proteins that were linked to disease in patients. One such protein, TBK1, is implicated in innate immunity and autophagy and may represent a therapeutic target.

Science, this issue p. 1436; see also p. 1422


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.

  • The full author list is included at the end of the manuscript.

View Full Text

Stay Connected to Science