biostudies-literatureTraylor MStroke AssociationIntramural NIH HHSEuropean Research CouncilNIA NIH HHSNHLBI NIH HHSMedical Research CouncilNational Institute for Health Research (NIHR)California Department of Fish and GameNINDS NIH HHSWellcome Trust383-394https://www.ebi.ac.uk/biostudies/studies/S-EPMC5366092biostudies-literatureUnknown81(3)<h4>Objective</h4>Genome-wide association studies (GWAS) have been successful at identifying associations with stroke and stroke subtypes, but have not yet identified any associations solely with small vessel stroke (SVS). SVS comprises one quarter of all ischemic stroke and is a major manifestation of cerebral small vessel disease, the primary cause of vascular cognitive impairment. Studies across neurological traits have shown that younger-onset cases have an increased genetic burden. We leveraged this increased genetic burden by performing an age-at-onset informed GWAS meta-analysis, including a large younger-onset SVS population, to identify novel associations with stroke.<h4>Methods</h4>We used a three-stage age-at-onset informed GWAS to identify novel genetic variants associated withAnnals of neurologyGenetic variation at 16q24.2 is associated with small vessel stroke.PMC5366092U01 NS069208MR/K013807/1095626R01 NS082285U01 HL096917R01 NS059727TSA2013/01TSA2010/01ERC 250157WT072952U01 HL096902CRC 1123, B3TSA 2013/01P30 AG010129R01 HL088521R01 AG008122Z01 AG007270R01 NS017950MR/K026992/1NF-SI-0512-10019U01 HL096814U01 HL096899250157U01 AG049505U01 HL096812NF-SI-0514-10027TSA 2010/01R01 NS085419Lindgren ACole JWThorleifsson GStefansson KCotlarciuc IMelander OInternational Stroke Genetics ConsortiumSacco RLRich SSRundek TChauhan GJimenez-Conde JKittner SJRost NSSchmidt RSpector TDde Bakker PIAnderson CDIkram MALee JMRadmanesh FSharma PWoo DMarkus HSJohnson JADichgans MXu HDebette SSlowik AHamilton-Bruce MATraylor MLemmens RJern CMETASTROKE, UK Young Lacunar DNA Study, NINDS Stroke Genetics Network, Neurology Working Group of the CHARGE ConsortiumWasssertheil-Smoller SGretarsdottir SPulit SLMill JFornage MNalls MAThorsteinsdottir UBell JTWorrall BBHeitsch LRothwell PMHannon EMeschia JFGrewal RPLewis CMLevi CArnett DKBoncoraglio GBBenavente ORYet IMalik RMcArdle PFWong QThijs VLangefeld CLongstreth WTSeshadri SRexrode KRosand JBis JCSudlow CLHanscombe KBLauner LJSaleheen DMitchell BDfalseGenetic variation at 16q24.2 is associated with small vessel stroke.<h4>Objective</h4>Genome-wide association studies (GWAS) have been successful at identifying associations with stroke and stroke subtypes, but have not yet identified any associations solely with small vessel stroke (SVS). SVS comprises one quarter of all ischemic stroke and is a major manifestation of cerebral small vessel disease, the primary cause of vascular cognitive impairment. Studies across neurological traits have shown that younger-onset cases have an increased genetic burden. We leveraged this increased genetic burden by performing an age-at-onset informed GWAS meta-analysis, including a large younger-onset SVS population, to identify novel associations with stroke.<h4>Methods</h4>We used a three-stage age-at-onset informed GWAS to identify novel genetic variants associated with2017-01-01T00:00:00Z2017 Mar2026-05-30T01:03:34.264Z2019-03-27T02:39:33ZS-EPMC53660922799704110.1002/ana.24840