Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways

Elizabeth T. Cirulli; Brittany N. Lasseigne; Slavé Petrovski; Peter C. Sapp; Patrick A. Dion; Claire S. Leblond; Julien Couthouis; Yi Fan Lu; Quanli Wang; Brian J. Krueger; Zhong Ren; Jonathan Keebler; Yujun Han; Shawn E. Levy; Braden E. Boone; Jack R. Wimbish; Lindsay L. Waite; Angela L. Jones; John P. Carulli; Aaron G. Day-Williams; John F. Staropoli; Winnie W. Xin; Alessandra Chesi; Alya R. Raphael; Diane McKenna-Yasek; Janet Cady; J. M.B.Vianney De Jong; Kevin P. Kenna; Bradley N. Smith; Simon Topp; Jack Miller; Athina Gkazi; Ammar Al-Chalabi; Leonard H. Van Den Berg; Jan Veldink; Vincenzo Silani; Nicola Ticozzi; Christopher E. Shaw; Robert H. Baloh; Stanley Appel; Ericka Simpson; Clotilde Lagier-Tourenne; Stefan M. Pulst; Summer Gibson; John Q. Trojanowski; Lauren Elman; Leo McCluskey; Murray Grossman; Neil A. Shneider; Wendy K. Chung; John M. Ravits; Jonathan D. Glass; Katherine B. Sims; Vivianna M. Van Deerlin; Tom Maniatis; Sebastian D. Hayes; Alban Ordureau; Sharan Swarup; John Landers; Frank Baas; Andrew S. Allen; Richard S. Bedlack; J. Wade Harper; Aaron D. Gitler; Guy A. Rouleau; Robert Brown; Matthew B. Harms; Gregory M. Cooper; Tim Harris; Richard M. Myers; David B. Goldstein; O. Hardiman; R. L. McLaughlin; L. Mazzini; I. P. Blair; K. L. Williams; G. A. Nicholson; S. Al-Sarraj; A. King; E. L. Scotter; C. Troakes; C. Vance; S. D'Alfonso; S. Duga; L. Corrado; A. L. ten Asbroek; D. Calini; C. Colombrita; A. Ratti; C. Tiloca; Z. Wu; S. Asress; M. Polak; F. Diekstra; W. van Rheenen; E. W. Danielson; C. Fallini; P. Keagle; E. A. Lewis; J. Kost; G. Sorarù; Cinzia Bertolin; G. Querin; B. Castellotti; C. Gellera; V. Pensato; F. Taroni; C. Cereda; S. Gagliardi; M. Ceroni; G. Lauria; J. de Belleroche; G. P. Comi; S. Corti; R. Del Bo; M. R. Turner; K. Talbot; H. Pall; K. E. Morrison; J. Esteban-Pérez; A. García-Redondo; J. L. Muñoz-Blanco

doi:10.1126/science.aaa3650

Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways

Elizabeth T. Cirulli, Brittany N. Lasseigne, Slavé Petrovski, Peter C. Sapp, Patrick A. Dion, Claire S. Leblond, Julien Couthouis, Yi Fan Lu, Quanli Wang, Brian J. Krueger, Zhong Ren, Jonathan Keebler, Yujun Han, Shawn E. Levy, Braden E. Boone, Jack R. Wimbish, Lindsay L. Waite, Angela L. Jones, John P. Carulli, Aaron G. Day-WilliamsJohn F. Staropoli, Winnie W. Xin, Alessandra Chesi, Alya R. Raphael, Diane McKenna-Yasek, Janet Cady, J. M.B.Vianney De Jong, Kevin P. Kenna, Bradley N. Smith, Simon Topp, Jack Miller, Athina Gkazi, Ammar Al-Chalabi, Leonard H. Van Den Berg, Jan Veldink, Vincenzo Silani, Nicola Ticozzi, Christopher E. Shaw, Robert H. Baloh, Stanley Appel, Ericka Simpson, Clotilde Lagier-Tourenne, Stefan M. Pulst, Summer Gibson, John Q. Trojanowski, Lauren Elman, Leo McCluskey, Murray Grossman, Neil A. Shneider, Wendy K. Chung, John M. Ravits, Jonathan D. Glass, Katherine B. Sims, Vivianna M. Van Deerlin, Tom Maniatis, Sebastian D. Hayes, Alban Ordureau, Sharan Swarup, John Landers, Frank Baas, Andrew S. Allen, Richard S. Bedlack, J. Wade Harper, Aaron D. Gitler, Guy A. Rouleau, Robert Brown, Matthew B. Harms, Gregory M. Cooper, Tim Harris, Richard M. Myers, David B. Goldstein, O. Hardiman, R. L. McLaughlin, L. Mazzini, I. P. Blair, K. L. Williams, G. A. Nicholson, S. Al-Sarraj, A. King, E. L. Scotter, C. Troakes, C. Vance, S. D'Alfonso, S. Duga, L. Corrado, A. L. ten Asbroek, D. Calini, C. Colombrita, A. Ratti, C. Tiloca, Z. Wu, S. Asress, M. Polak, F. Diekstra, W. van Rheenen, E. W. Danielson, C. Fallini, P. Keagle, E. A. Lewis, J. Kost, G. Sorarù, Cinzia Bertolin, G. Querin, B. Castellotti, C. Gellera, V. Pensato, F. Taroni, C. Cereda, S. Gagliardi, M. Ceroni, G. Lauria, J. de Belleroche, G. P. Comi, S. Corti, R. Del Bo, M. R. Turner, K. Talbot, H. Pall, K. E. Morrison, J. Esteban-Pérez, A. García-Redondo, J. L. Muñoz-Blanco

Dipartimento di Scienze della Salute

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

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.

Lingua originale	Inglese
pagine (da-a)	1436-1441
Numero di pagine	6
Rivista	Science
Volume	347
Numero di pubblicazione	6229
DOI	https://doi.org/10.1126/science.aaa3650
Stato di pubblicazione	Pubblicato - 27 mar 2015

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10.1126/science.aaa3650

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Cirulli, E. T., Lasseigne, B. N., Petrovski, S., Sapp, P. C., Dion, P. A., Leblond, C. S., Couthouis, J., Lu, Y. F., Wang, Q., Krueger, B. J., Ren, Z., Keebler, J., Han, Y., Levy, S. E., Boone, B. E., Wimbish, J. R., Waite, L. L., Jones, A. L., Carulli, J. P., ... Muñoz-Blanco, J. L. (2015). Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways. Science, 347(6229), 1436-1441. https://doi.org/10.1126/science.aaa3650

@article{390a8185dc164eb693b2a7f0c47f3738,

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.",

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 Lu, {Yi Fan} 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 {De Jong}, {J. M.B.Vianney} 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 Ravits, {John M.} and Glass, {Jonathan D.} and Sims, {Katherine B.} and {Van Deerlin}, {Vivianna M.} and Tom Maniatis and Hayes, {Sebastian D.} and Alban Ordureau and Sharan Swarup and John Landers and Frank Baas and Allen, {Andrew S.} and Bedlack, {Richard S.} and Harper, {J. Wade} and Gitler, {Aaron D.} and Rouleau, {Guy A.} and Robert Brown and Harms, {Matthew B.} and Cooper, {Gregory M.} and Tim Harris and Myers, {Richard M.} and Goldstein, {David B.} and O. Hardiman and McLaughlin, {R. L.} and L. Mazzini and Blair, {I. P.} and Williams, {K. L.} and Nicholson, {G. A.} and S. Al-Sarraj and A. King and Scotter, {E. L.} and C. Troakes and C. Vance and S. D'Alfonso and S. Duga and L. Corrado and {ten Asbroek}, {A. L.} and D. Calini and C. Colombrita and A. Ratti and C. Tiloca and Z. Wu and S. Asress and M. Polak and F. Diekstra and {van Rheenen}, W. and Danielson, {E. W.} and C. Fallini and P. Keagle and Lewis, {E. A.} and J. Kost and G. Sorar{\`u} and Cinzia Bertolin and G. Querin and B. Castellotti and C. Gellera and V. Pensato and F. Taroni and C. Cereda and S. Gagliardi and M. Ceroni and G. Lauria and {de Belleroche}, J. and Comi, {G. P.} and S. Corti and {Del Bo}, R. and Turner, {M. R.} and K. Talbot and H. Pall and Morrison, {K. E.} and J. Esteban-P{\'e}rez and A. Garc{\'i}a-Redondo and Mu{\~n}oz-Blanco, {J. L.}",

year = "2015",

month = mar,

day = "27",

doi = "10.1126/science.aaa3650",

language = "English",

volume = "347",

pages = "1436--1441",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6229",

}

Cirulli, ET, Lasseigne, BN, Petrovski, S, Sapp, PC, Dion, PA, Leblond, CS, Couthouis, J, Lu, YF, Wang, Q, Krueger, BJ, Ren, Z, Keebler, J, Han, Y, Levy, SE, Boone, BE, Wimbish, JR, Waite, LL, Jones, AL, Carulli, JP, Day-Williams, AG, Staropoli, JF, Xin, WW, Chesi, A, Raphael, AR, McKenna-Yasek, D, Cady, J, De Jong, JMBV, Kenna, KP, Smith, BN, Topp, S, Miller, J, Gkazi, A, Al-Chalabi, A, Van Den Berg, LH, Veldink, J, Silani, V, Ticozzi, N, Shaw, CE, Baloh, RH, Appel, S, Simpson, E, Lagier-Tourenne, C, Pulst, SM, Gibson, S, Trojanowski, JQ, Elman, L, McCluskey, L, Grossman, M, Shneider, NA, Chung, WK, Ravits, JM, Glass, JD, Sims, KB, Van Deerlin, VM, Maniatis, T, Hayes, SD, Ordureau, A, Swarup, S, Landers, J, Baas, F, Allen, AS, Bedlack, RS, Harper, JW, Gitler, AD, Rouleau, GA, Brown, R, Harms, MB, Cooper, GM, Harris, T, Myers, RM, Goldstein, DB, Hardiman, O, McLaughlin, RL, Mazzini, L, Blair, IP, Williams, KL, Nicholson, GA, Al-Sarraj, S, King, A, Scotter, EL, Troakes, C, Vance, C, D'Alfonso, S, Duga, S, Corrado, L, ten Asbroek, AL, Calini, D, Colombrita, C, Ratti, A, Tiloca, C, Wu, Z, Asress, S, Polak, M, Diekstra, F, van Rheenen, W, Danielson, EW, Fallini, C, Keagle, P, Lewis, EA, Kost, J, Sorarù, G, Bertolin, C, Querin, G, Castellotti, B, Gellera, C, Pensato, V, Taroni, F, Cereda, C, Gagliardi, S, Ceroni, M, Lauria, G, de Belleroche, J, Comi, GP, Corti, S, Del Bo, R, Turner, MR, Talbot, K, Pall, H, Morrison, KE, Esteban-Pérez, J, García-Redondo, A & Muñoz-Blanco, JL 2015, 'Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways', Science, vol. 347, n. 6229, pagg. 1436-1441. https://doi.org/10.1126/science.aaa3650

TY - JOUR

T1 - Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways

AU - Cirulli, Elizabeth T.

AU - Lasseigne, Brittany N.

AU - Petrovski, Slavé

AU - Sapp, Peter C.

AU - Dion, Patrick A.

AU - Leblond, Claire S.

AU - Couthouis, Julien

AU - Lu, Yi Fan

AU - Wang, Quanli

AU - Krueger, Brian J.

AU - Ren, Zhong

AU - Keebler, Jonathan

AU - Han, Yujun

AU - Levy, Shawn E.

AU - Boone, Braden E.

AU - Wimbish, Jack R.

AU - Waite, Lindsay L.

AU - Jones, Angela L.

AU - Carulli, John P.

AU - Day-Williams, Aaron G.

AU - Staropoli, John F.

AU - Xin, Winnie W.

AU - Chesi, Alessandra

AU - Raphael, Alya R.

AU - McKenna-Yasek, Diane

AU - Cady, Janet

AU - De Jong, J. M.B.Vianney

AU - Kenna, Kevin P.

AU - Smith, Bradley N.

AU - Topp, Simon

AU - Miller, Jack

AU - Gkazi, Athina

AU - Al-Chalabi, Ammar

AU - Van Den Berg, Leonard H.

AU - Veldink, Jan

AU - Silani, Vincenzo

AU - Ticozzi, Nicola

AU - Shaw, Christopher E.

AU - Baloh, Robert H.

AU - Appel, Stanley

AU - Simpson, Ericka

AU - Lagier-Tourenne, Clotilde

AU - Pulst, Stefan M.

AU - Gibson, Summer

AU - Trojanowski, John Q.

AU - Elman, Lauren

AU - McCluskey, Leo

AU - Grossman, Murray

AU - Shneider, Neil A.

AU - Chung, Wendy K.

AU - Ravits, John M.

AU - Glass, Jonathan D.

AU - Sims, Katherine B.

AU - Van Deerlin, Vivianna M.

AU - Maniatis, Tom

AU - Hayes, Sebastian D.

AU - Ordureau, Alban

AU - Swarup, Sharan

AU - Landers, John

AU - Baas, Frank

AU - Allen, Andrew S.

AU - Bedlack, Richard S.

AU - Harper, J. Wade

AU - Gitler, Aaron D.

AU - Rouleau, Guy A.

AU - Brown, Robert

AU - Harms, Matthew B.

AU - Cooper, Gregory M.

AU - Harris, Tim

AU - Myers, Richard M.

AU - Goldstein, David B.

AU - Hardiman, O.

AU - McLaughlin, R. L.

AU - Mazzini, L.

AU - Blair, I. P.

AU - Williams, K. L.

AU - Nicholson, G. A.

AU - Al-Sarraj, S.

AU - King, A.

AU - Scotter, E. L.

AU - Troakes, C.

AU - Vance, C.

AU - D'Alfonso, S.

AU - Duga, S.

AU - Corrado, L.

AU - ten Asbroek, A. L.

AU - Calini, D.

AU - Colombrita, C.

AU - Ratti, A.

AU - Tiloca, C.

AU - Wu, Z.

AU - Asress, S.

AU - Polak, M.

AU - Diekstra, F.

AU - van Rheenen, W.

AU - Danielson, E. W.

AU - Fallini, C.

AU - Keagle, P.

AU - Lewis, E. A.

AU - Kost, J.

AU - Sorarù, G.

AU - Bertolin, Cinzia

AU - Querin, G.

AU - Castellotti, B.

AU - Gellera, C.

AU - Pensato, V.

AU - Taroni, F.

AU - Cereda, C.

AU - Gagliardi, S.

AU - Ceroni, M.

AU - Lauria, G.

AU - de Belleroche, J.

AU - Comi, G. P.

AU - Corti, S.

AU - Del Bo, R.

AU - Turner, M. R.

AU - Talbot, K.

AU - Pall, H.

AU - Morrison, K. E.

AU - Esteban-Pérez, J.

AU - García-Redondo, A.

AU - Muñoz-Blanco, J. L.

PY - 2015/3/27

Y1 - 2015/3/27

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84945749129&partnerID=8YFLogxK

U2 - 10.1126/science.aaa3650

DO - 10.1126/science.aaa3650

M3 - Article

SN - 0036-8075

VL - 347

SP - 1436

EP - 1441

JO - Science

JF - Science

IS - 6229

ER -

Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways

Abstract

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