{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Nicolas A"],"funding":["BLRD VA","Intramural NIH HHS","NIA NIH HHS","NIEHS NIH HHS","NHLBI NIH HHS","Motor Neurone Disease Association","Rosetrees","Academy of Medical Sciences","Medical Research Foundation","European Research Council","Medical Research Council","NIMHD NIH HHS","National Institute for Health Research (NIHR)","MRF_","NINDS NIH HHS","Wellcome Trust"],"pagination":["1267-1288"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5867896"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["97(6)"],"pubmed_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 surviva"],"journal":["Neuron"],"pubmed_title":["Genome-wide Analyses Identify KIF5A as a Novel ALS Gene."],"pmcid":["PMC5867896"],"funding_grant_id":["UKDRI-6001","P30 AG013846","MCLAUGHLIN/OCT15/957-799","MC_PC_17115","MR/L021803/1","Z01 AG000949","P50 AG005146","R56 NS061867","P01 NS084974","FRATTA/JAN15/946-795","SMITH/APR16/847-791","MR/M008606/1","M599","P01 AG017586","R35 NS097261","MALASPINA/APR13/817-791","I01 BX002466","SHAW/NOV14/985-797","340429","SGL018\\1007","G0600974","R01 NS073873","SMITH/OCT16/888-792","MRF-060-0003-RG-SMITH","NF-SI-0512-10082","MR/K01014X/1","SHAW/APR15/933-794","K23 ES027221","U54 NS092091","CL-2015-04-001","NF-SI-0617-10077","U54 NS091046","MR/L501529/1","G0500289","K25 HL121295","TURNER/OCT18/989-797","R01 MD009164","ZIA AG000933","MR/L016397/1","TURNER/JAN13/944-795","ALCHALABI-DOBSON/APR14/829-791","G0900688","MR/R024804/1","R01 NS061867"],"pubmed_authors":["Dardiotis E","Corongiu D","Benigni M","Twine NA","Bedlack R","Van Damme P","Blair IP","Floeter MK","Vourch P","Rogaeva E","SLAGEN Consortium","Malaspina A","Mandrioli J","Dominov JA","Ten Asbroek ALMA","Harms MB","Marrosu MG","Mill J","McLaughlin R","Cuccu S","Lee EB","Al Kheifat A","Soraru G","Sidle KC","Van Deerlin VM","Valori M","Middelkoop B","Casale F","Jenkins L","Caponnetto C","Bowser R","Smith BN","van Vugt J","Petrucci A","Esteban-Perez J","Redondo AG","Lima L","Taylor JP","Hamdalla H","Landi F","Drory VE","Tazelaar G","Cooper-Knock J","Lu YF","Salvi F","Pickering-Brown S","Kowall NW","van Eijk K","Pensato V","Barohn R","Fogh I","Andersen P","Couratier P","Penco S","Vance C","Cau TB","van Damme P","Gagliardi S","Ravits JM","Johnson JO","Del Bo R","Cox GA","Tremolizzo L","Tienari P","Cooper GM","Marrali G","Jansson L","Origone P","Waite LL","Clavelou P","Inghilleri M","Zuchner S","Lunetta C","Kolb SJ","Fuda G","Al-Sarraj S","Marrosu F","Ludolph AC","Finkbeiner S","Morrison KE","Arcila-Londono X","Glass JD","Castellotti B","ITALSGEN Consortium","Harris T","Pioro E","Goutman SA","Sapp PC","Dion PA","Rothstein JD","Ostrow LW","Abramzon Y","Veldink JH","Neto MM","van den Berg L","Manera U","Gitler AD","Lauria G","Maragakis NJ","Feldman EL","Carrera P","Mancardi G","Cammarosano S","Broach J","Eicher JD","Raphael AR","Pioro EP","Faghri F","Van Eyk JE","Gkazi AS","Fasano A","Gwathmey K","Mouzat K","Logroscino G","Marinou K","McCauley J","Fifita JA","Hardiman O","Bartolomei I","MacGowan DJL","Colombrita C","Glass J","Melis M","Lumbroso S","Zollino M","Borghero G","Penny M","Nalls MA","Tiloca C","Bruijn L","Mora JS","Ren Z","Campbell RH","Shaw C","Han Y","Berry JD","Piccirillo G","Shneider NA","Andersen PM","Shaw P","Hammell MG","Tanel R","Conte A","Sims KB","Basak AN","Gibbs JR","Weishaupt JH","Shaw PJ","Iacoangeli A","Troakes C","Boone BE","Chia R","Piras V","Allen AS","La Bella V","Newhouse S","Project MinE ALS Sequencing Consortium","Pal S","Dekker A","Wyman SK","De Marchi F","Svendsen CN","Rampersaud E","Arepalli S","Maniatis T","Robberecht W","Giannini F","Moglia C","Hussain S","Pinter GL","ALS Sequencing Consortium","Baxi E","Meitinger T","Meininger V","D'Alfonso S","Arosio A","Bertolin C","Battistini S","Rollinson S","Dunckley TL","Loi D","Brady CB","Trivedi J","Hornstein E","Nicholson GA","Petrovski S","Kiernan M","Levy SE","Ferrarese C","Lasseigne BN","Hardy J","Goldstein DB","Hide W","Clayman C","Troncoso JC","Munoz-Blanco JL","Maderna L","McLaughlin RL","Luigetti M","Occhineri P","Lacomis D","Pliner HA","Singleton AB","Topp SD","Grassano M","de Belleroche J","Lagrange E","Heiman-Patterson T","Abhyankar A","Chio A","Cooley A","Parish LD","Al-Chalabi A","Van Eyk J","Sproviero W","Caredda C","Asress S","Musunuri RL","Khan S","Gibson S","Rivera AM","Simone I","Chesi A","Williams KL","Van Es MA","Kwan J","Logullo FO","Elman L","Zinman L","Cereda C","Bauer DC","Staropoli JF","Moisse M","Katz J","Walk D","Morrison K","Ticca A","Gibson SB","Moreno CAM","Gellera C","Caress J","Geiger JT","Xin WW","Ilardi A","Verde F","Hayes SD","Peverelli S","Pirisi A","Mosca L","Silani V","Taroni F","Myers RM","Kirby J","Heiman-Patterson TD","Kamel F","Kooyman M","Sabatelli M","Sideri R","Ceroni M","Bernard E","Lemasson G","Scholz SW","Garcia-Redondo A","van den Berg LH","Myllykangas L","Kenna KP","Benatar M","Camu W","Barberis M","Guy N","Hernandez DG","Trojanowski JQ","MacGowan DJ","Cannas A","McKenna-Yasek D","Santarelli M","Baas F","Pamphlett R","Shaw CE","Day-Williams AG","Siciliano G","Wuu J","Pani C","Brice A","Pugliatti M","Trojsi F","Puddu R","Sareen D","Corrado L","Jones AL","Calvo A","Renton AE","Wallace M","Ticozzi N","Lattante S","Appel SH","Murphy NA","Manousakis G","Spataro R","Kamalakaran S","Jackson C","Keebler J","Gerhard G","Pisano F","Zody MC","Femiano C","Weber M","Burns T","van der Spek R","Danel V","Evani US","Van Den Bosch L","Poletti B","Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Consortium","Mora G","de Carvalho M","French ALS Consortium","Polak M","van Es M","Cirulli ET","Veldink J","Couthouis J","NYGC ALS Consortium","Simpson E","Zhang J","Ratti A","Broach JR","Boylan KB","Bedlack RS","Volanti P","Floris G","Talbot K","Genomic Translation for ALS Care (GTAC) Consortium","Riva N","Canosa A","Landers J","Costantino E","McMillan C","Kaye J","Fraenkel E","Turner MR","Miller TM","Goutman S","Cudkowicz M","Van Eijk KR","Querin G","Comi GP","Simmons Z","Brown RH","Thompson LM","Landers JE","Kenna A","Orrell RW","Conforti FL","Wimbish JR","Cavallaro S","Carulli JP","Schule R","Tedeschi G","Nath A","Chung WK","Van der Spek RA","Colletti T","Mazzini L","van Vugt JJFA","Kenna K","Besson G","van Rheenen W","Ealing J","Corcia P","Patsopoulos NA","Sherman A","Monsurro MR","Gotkine M","Traynor BJ","Zaitlen N","Appel S","Ricci C","Mandich P","Corbo M","Pinto S","Heckmann J","Statland J","Rademakers R","Le Ber I","Wu G","Wang L","So Y","Wang Q","Ferrucci L","Rouleau GA","Kenna BJ","Ravits J","Pulst SM","Strom TM","Ortu E","Restagno G","Simone IL","Wyman S","Shankaracharya","Pardina JM","Keagle P","Pulit S","Stone DJ","Drory V","Answer ALS Foundation","Murru MR","Laaksovirta H","Phatnani H","Marangi G","Swenson A","Fratta P","Ossola I","Ding J","Tranquilli S","Filosto M","Maiser S","Zatz M","Nicolas A","LeNail A","Fini N","Shatunov A","Dubnau J","Messina S","Milia A","Corti S","Capasso M","Krueger BJ","Brunetti M","King A","Baloh RH","Van Blitterswijk M","Chandran S","Brown R"],"additional_accession":[]},"is_claimable":false,"name":"Genome-wide Analyses Identify KIF5A as a Novel ALS Gene.","description":"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 surviva","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Mar","modification":"2026-04-29T03:53:33.169Z","creation":"2019-06-06T19:11:40Z"},"accession":"S-EPMC5867896","cross_references":{"pubmed":["29566793"],"doi":["10.1016/j.neuron.2018.02.027"]}}