Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways

ET Cirulli; BN Lasseigne; S Petrovski; PC Sapp; PA Dion; CS Leblond; J Couthouis; YF Lu; Q Wang; BJ Krueger; Z Ren; J Keebler; Y Han; SE Levy; BE Boone; JR Wimbish; LL Waite; AL Jones; JP Carulli; AG Day-Williams; JF Staropoli; WW Xin; A Chesi; AR Raphael; D McKenna-Yasek; J Cady; JMBV De Jong; KP Kenna; BN Smith; S Topp; J Miller; A Gkazi; A Al-Chalabi; LH Van Den Berg; J Veldink; V Silani; N Ticozzi; CE Shaw; RH Baloh; S Appel; E Simpson; C Lagier-Tourenne; SM Pulst; S Gibson; JQ Trojanowski; L Elman; L McCluskey; M Grossman; NA Shneider; WK Chung; JM Ravits; JD Glass; KB Sims; VM Van Deerlin; T Maniatis; SD Hayes; A Ordureau; S Swarup; J Landers; F Baas; AS Allen; RS Bedlack; JW Harper; AD Gitler; GA Rouleau; R Brown; MB Harms; GM Cooper; T Harris; RM Myers; DB Goldstein; O Hardiman; RL McLaughlin; L Mazzini; IP Blair; KL Williams; GA Nicholson; S Al-Sarraj; A King; EL Scotter; C Troakes; C Vance; S D'Alfonso; S Duga; L Corrado; AL ten Asbroek; D Calini; C Colombrita; A Ratti; C Tiloca; Z Wu; S Asress; M Polak; F Diekstra; W van Rheenen; EW Danielson; C Fallini; P Keagle; EA Lewis; J Kost

Journal article

Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways

ET Cirulli, BN Lasseigne, S Petrovski, PC Sapp, PA Dion, CS Leblond, J Couthouis, YF Lu, Q Wang, BJ Krueger, Z Ren, J Keebler, Y Han, SE Levy, BE Boone, JR Wimbish, LL Waite, AL Jones, JP Carulli, AG Day-Williams Show all

Science | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2015

DOI: 10.1126/science.aaa3650

Abstract

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..

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