Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways
Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways
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.
1436-1441
Cirulli, E.T.
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Lasseigne, B.N.
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Petrovski, S.
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Sapp, P.C.
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Dion, P.A.
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Leblond, C.S.
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Couthouis, J.
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Lu, Y.-F.
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Wang, Q.
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Krueger, B.J.
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Ren, Z.
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Keebler, J.
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Han, Y.
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Levy, S.E.
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Boone, B.E.
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Wimbish, J.R.
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Waite, L.L.
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Jones, A.L.
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Carulli, J.P.
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Day-Williams, A.G.
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Staropoli, J.F.
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Xin, W.W.
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Chesi, A.
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Raphael, A.R.
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McKenna-Yasek, D.
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Cady, J.
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Vianney de Jong, J. M. B.
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Kenna, K. P.
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Smith, B. N.
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Topp, S.
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Miller, J.
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Gkazi, A.
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Al-Chalabi, A.
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van den Berg, L.H.
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Veldink, J.
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Silani, V.
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Ticozzi, N.
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Shaw, C. E.
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Baloh, R. H.
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Appel, S.
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Simpson, E.
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Pulst, S.M.
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Gibson, S.
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Trojanowski, J. Q.
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Elman, L.
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McCluskey, L.
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Grossman, M.
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Shneider, N.A.
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Chung, W. K.
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Ravits, J. M.
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Glass, J. D.
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Sims, K. B.
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Van Deerlin, V.M.
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Maniatis, T.
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Hayes, S.D.
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Ordureau, A.
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Swarup, S.
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Landers, J.
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Baas, F.
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Allen, A.S.
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Harper, J.W.
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Gitler, A.D.
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Rouleau, G. A.
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Brown, R.
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Harms, M.B.
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Cooper, G.M.
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Harris, T.
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Myers, R.M.
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Goldstein, D.B.
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Morrison, K.E.
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27 March 2015
Cirulli, E.T.
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Lasseigne, B.N.
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Petrovski, S.
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Sapp, P.C.
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Dion, P.A.
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Leblond, C.S.
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Couthouis, J.
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Lu, Y.-F.
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Wang, Q.
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Krueger, B.J.
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Ren, Z.
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Keebler, J.
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Han, Y.
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Levy, S.E.
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Boone, B.E.
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Wimbish, J.R.
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Waite, L.L.
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Jones, A.L.
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Carulli, J.P.
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Day-Williams, A.G.
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Staropoli, J.F.
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Xin, W.W.
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Chesi, A.
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Raphael, A.R.
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McKenna-Yasek, D.
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Cady, J.
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Vianney de Jong, J. M. B.
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Kenna, K. P.
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Smith, B. N.
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Topp, S.
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Miller, J.
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Gkazi, A.
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Al-Chalabi, A.
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van den Berg, L.H.
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Veldink, J.
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Silani, V.
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Ticozzi, N.
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Shaw, C. E.
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Baloh, R. H.
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Appel, S.
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Simpson, E.
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Lagier-Tourenne, C.
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Pulst, S.M.
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Gibson, S.
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Trojanowski, J. Q.
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Elman, L.
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McCluskey, L.
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Grossman, M.
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Shneider, N.A.
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Chung, W. K.
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Ravits, J. M.
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Glass, J. D.
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Sims, K. B.
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Van Deerlin, V.M.
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Maniatis, T.
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Hayes, S.D.
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Ordureau, A.
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Swarup, S.
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Landers, J.
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Baas, F.
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Gitler, A.D.
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Rouleau, G. A.
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Brown, R.
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Harms, M.B.
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Cooper, G.M.
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Harris, T.
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Myers, R.M.
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Goldstein, D.B.
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Morrison, K.E.
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