Genome-wide Analyses Identify KIF5A as a Novel ALS GeneCitation formats

  • Authors:
  • ITALSGEN Consortium

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Genome-wide Analyses Identify KIF5A as a Novel ALS Gene. / ITALSGEN Consortium.

In: Neuron, Vol. 97, No. 6, 2018, p. 1268-1283.e6.

Research output: Contribution to journalArticle

Harvard

ITALSGEN Consortium 2018, 'Genome-wide Analyses Identify KIF5A as a Novel ALS Gene', Neuron, vol. 97, no. 6, pp. 1268-1283.e6. https://doi.org/10.1016/j.neuron.2018.02.027

APA

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Author

ITALSGEN Consortium. / Genome-wide Analyses Identify KIF5A as a Novel ALS Gene. In: Neuron. 2018 ; Vol. 97, No. 6. pp. 1268-1283.e6.

Bibtex

@article{dba61de72a164b3797dd5732a53adf56,
title = "Genome-wide Analyses Identify KIF5A as a Novel ALS Gene",
abstract = "To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.",
author = "{ITALSGEN Consortium} and Aude Nicolas and Kenna, {Kevin P} and Renton, {Alan E} and Nicola Ticozzi and Faraz Faghri and Ruth Chia and Dominov, {Janice A} and Kenna, {Brendan J} and Nalls, {Mike A} and Pamela Keagle and Rivera, {Alberto M} and {van Rheenen}, Wouter and Murphy, {Natalie A} and {van Vugt}, {Joke J F A} and Geiger, {Joshua T} and {Van der Spek}, {Rick A} and Pliner, {Hannah A} and Shankaracharya and Smith, {Bradley N} and Giuseppe Marangi and Topp, {Simon D} and Yevgeniya Abramzon and Gkazi, {Athina Soragia} and Eicher, {John D} and Aoife Kenna and Gabriele Mora and Andrea Calvo and Letizia Mazzini and Nilo Riva and Jessica Mandrioli and Claudia Caponnetto and Stefania Battistini and Paolo Volanti and {La Bella}, Vincenzo and Conforti, {Francesca L} and Giuseppe Borghero and Sonia Messina and Simone, {Isabella L} and Francesca Trojsi and Fabrizio Salvi and Logullo, {Francesco O} and Sandra D'Alfonso and Lucia Corrado and Margherita Capasso and Luigi Ferrucci and Moreno, {Cristiane de Araujo Martins} and John Ealing and Hisham Hamdalla and Sara Rollinson and Stuart Pickering-Brown",
note = "Copyright {\circledC} 2018 Elsevier Inc. All rights reserved.",
year = "2018",
doi = "10.1016/j.neuron.2018.02.027",
language = "English",
volume = "97",
pages = "1268--1283.e6",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "6",

}

RIS

TY - JOUR

T1 - Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

AU - ITALSGEN Consortium

AU - Nicolas, Aude

AU - Kenna, Kevin P

AU - Renton, Alan E

AU - Ticozzi, Nicola

AU - Faghri, Faraz

AU - Chia, Ruth

AU - Dominov, Janice A

AU - Kenna, Brendan J

AU - Nalls, Mike A

AU - Keagle, Pamela

AU - Rivera, Alberto M

AU - van Rheenen, Wouter

AU - Murphy, Natalie A

AU - van Vugt, Joke J F A

AU - Geiger, Joshua T

AU - Van der Spek, Rick A

AU - Pliner, Hannah A

AU - Shankaracharya, null

AU - Smith, Bradley N

AU - Marangi, Giuseppe

AU - Topp, Simon D

AU - Abramzon, Yevgeniya

AU - Gkazi, Athina Soragia

AU - Eicher, John D

AU - Kenna, Aoife

AU - Mora, Gabriele

AU - Calvo, Andrea

AU - Mazzini, Letizia

AU - Riva, Nilo

AU - Mandrioli, Jessica

AU - Caponnetto, Claudia

AU - Battistini, Stefania

AU - Volanti, Paolo

AU - La Bella, Vincenzo

AU - Conforti, Francesca L

AU - Borghero, Giuseppe

AU - Messina, Sonia

AU - Simone, Isabella L

AU - Trojsi, Francesca

AU - Salvi, Fabrizio

AU - Logullo, Francesco O

AU - D'Alfonso, Sandra

AU - Corrado, Lucia

AU - Capasso, Margherita

AU - Ferrucci, Luigi

AU - Moreno, Cristiane de Araujo Martins

AU - Ealing, John

AU - Hamdalla, Hisham

AU - Rollinson, Sara

AU - Pickering-Brown, Stuart

N1 - Copyright © 2018 Elsevier Inc. All rights reserved.

PY - 2018

Y1 - 2018

N2 - To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.

AB - To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.

U2 - 10.1016/j.neuron.2018.02.027

DO - 10.1016/j.neuron.2018.02.027

M3 - Article

VL - 97

SP - 1268-1283.e6

JO - Neuron

JF - Neuron

SN - 0896-6273

IS - 6

ER -