@article{26a257a8c93549f8a18c2528e641419d,
title = "Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways",
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 key role of the autophagic pathway in ALS and suggest specific targets for therapeutic intervention.",
keywords = "Adaptor Proteins, Signal Transducing, Adolescent, Adult, Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis, Autophagy, Exome, Female, Genes, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Protein Binding, Protein-Serine-Threonine Kinases, Risk, Sequence Analysis, DNA, Transcription Factor TFIIIA, Young Adult",
author = "Cirulli, {Elizabeth T} and Lasseigne, {Brittany N} and Slav{\'e} Petrovski and Sapp, {Peter C} and Dion, {Patrick A} and Leblond, {Claire S} and Julien Couthouis and Yi-Fan Lu and Quanli Wang and Krueger, {Brian J} and Zhong Ren and Jonathan Keebler and Yujun Han and Levy, {Shawn E} and Boone, {Braden E} and Wimbish, {Jack R} and Waite, {Lindsay L} and Jones, {Angela L} and Carulli, {John P} and Day-Williams, {Aaron G} and Staropoli, {John F} and Xin, {Winnie W} and Alessandra Chesi and Raphael, {Alya R} and Diane McKenna-Yasek and Janet Cady and {Vianney de Jong}, {J M B} and Kenna, {Kevin P} and Smith, {Bradley N} and Simon Topp and Jack Miller and Athina Gkazi and Ammar Al-Chalabi and {van den Berg}, {Leonard H} and Jan Veldink and Vincenzo Silani and Nicola Ticozzi and Shaw, {Christopher E} and Baloh, {Robert H} and Stanley Appel and Ericka Simpson and Clotilde Lagier-Tourenne and Pulst, {Stefan M} and Summer Gibson and Trojanowski, {John Q} and Lauren Elman and Leo McCluskey and Murray Grossman and Shneider, {Neil A} and Chung, {Wendy K} and {FALS Sequencing Consortium}",
note = "Copyright {\textcopyright} 2015, American Association for the Advancement of Science.",
year = "2015",
month = mar,
day = "27",
doi = "10.1126/science.aaa3650",
language = "English (US)",
volume = "347",
pages = "1436--41",
journal = "Science (New York, N.Y.)",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6229",
}