biostudies-literatureRannikmae KNCATS NIH HHSNIA NIH HHSNIDDK NIH HHSNHLBI NIH HHSNational Institute for Health Research (NIHR)NINDS NIH HHS1829-1839https://www.ebi.ac.uk/biostudies/studies/S-EPMC5664302biostudies-literatureUnknown89(17)<h4>Objective</h4>To determine whether common variants in familial cerebral small vessel disease (SVD) genes confer risk of sporadic cerebral SVD.<h4>Methods</h4>We meta-analyzed genotype data from individuals of European ancestry to determine associations of common single nucleotide polymorphisms (SNPs) in 6 familial cerebral SVD genes (<i>COL4A1</i>, <i>COL4A2</i>, <i>NOTCH3</i>, <i>HTRA1</i>, <i>TREX1</i>, and <i>CECR1</i>) with intracerebral hemorrhage (ICH) (deep, lobar, all; 1,878 cases, 2,830 controls) and ischemic stroke (IS) (lacunar, cardioembolic, large vessel disease, all; 19,569 cases, 37,853 controls). We applied data quality filters and set statistical significance thresholds accounting for linkage disequilibrium and multiple testing.<h4>Results</h4>A locus in <i>COL4A2</i> Neurology<i>COL4A2</i> is associated with lacunar ischemic stroke and deep ICH: Meta-analyses among 21,500 cases and 40,600 controls.PMC5664302U01 NS069208U01 AG009740K23 NS086873U01 NS036695UL1 TR001863KL2 TR001429R01 NS082285NF-SI-0512-10019R01 NS059727P30 DK072488K23 NS064052K23 NS100816R01 HL088521R01 NS086905Kappelle LJPsaty BMWei-Min Chen FMaguire JSacco RLWood NWSeiler SMathew CGMosley THWiggins KLRost NSAnderson CDWang XQBsc CSHolliday EGGwinn KTrembath RCWeir DRWoo DHankey GJBlackwell JMPoole DCuadrado-Godia EXu HBartz TMStrauch KPalmer CNSparks MJBerger KGretarsdottir SRedfors PJackson RDThorsteinsdottir UWloch-Kopec DSchmidt COKardia SLWaldenberger MSchurks MZhao WBattey TThorsteindottir UGiese AKRibases MSivakumaran VHoward GDonnelly PBlanton SHMeschia JFLevi CViswanathan ACRannikmae KBoncoraglio GBCheng YCKleindorfer DORasheed ALevi CRLabovitz DBrown MARodriguez-Campello APera JWong QLaurie CCStine OCLaurie CARabionet RRexrode KBis JCBevan SFaul JDLee CHRose LMRosenbaum DDeStefano ALArsava EMP JMitchell BDFernandez-Cadenas IPeters ASturm JThorleifsson GCotlarciuc Ide Bakker PIWRich SSBurgess AIRundek TRolfs ALee JMHorenstein RBDong CAy HPalleja XESpencer CCGieger CSharma PDawson JGrittner UWassertheil-Smoller SStroke Genetics Network (SiGN), METASTROKE Collaboration, and International Stroke Genetics Consortium (ISGC)Johnson JAMeisinger CShuldiner ARDichgans MAlgra ADuggan DJBramon ELeys DVicente AMTraylor MLemmens RTajuddin SMMuller-Nurasyid MFornage MHochberg MCLiu JRothwell PMKissela BMHolliday EScott RDave TMontaner JArnett DKWoodfield RMalik RPedersen AChapman Smith SNGiralt-Steinhauer EAbrantes PCarrera CLauner LJO'Donnell MSaleheen DGonzalez HMTrompet SLindgren ADuncanson AMelander OWalters MAttia JRSawcer SJPlomin RPapanicolaou GJChasman DIOis AWilliams SRMcClure LAPeddareddygari LRIkram MAFerro JMEngstrom GO'Connell JRDoheny KFPare GDelavaran HCorvin ASlowik ACruchaga CRoquer JJern CJood KChen WMPulit SLFurie KChong MFrossard PMNalls MAWorrall BBIrvin MRSalomaa VValant VGamble DMSanchez-Mora CTatlisumak TDeloukas PDell CASmith JAFalcone GJKaplan RBenavente ORReiner APMcArdle PFSilver BAchterberg SIlinca AOliveira SAHan BRaffeld MRKeene KLCole JWWu OMcDonough CWStanne TStefansson KHiggins PClarke RGoris AAmouyel PChauhan GSchmidt HWang LJimenez-Conde JRobberecht WZonderman ABRautanen AKittner SJSchmidt RSoderholm MGustafsson SHopewell JCRadmanesh FBarroso IMola-Caminal MMarkus HSCasas JPDebette SKahn MSEvans MKSale MMBattey TWManichaikul AAttia JBrown RDCloonan LKHeitsch LMillar HIngelsson EKoblar SBiffi AGrewal RPSegal HCJankowski JRyan KASudlow CLMThijs VTalbert RLSeshadri SLongstreth WTRosand JLichtner Pfalse<i>COL4A2</i> is associated with lacunar ischemic stroke and deep ICH: Meta-analyses among 21,500 cases and 40,600 controls.<h4>Objective</h4>To determine whether common variants in familial cerebral small vessel disease (SVD) genes confer risk of sporadic cerebral SVD.<h4>Methods</h4>We meta-analyzed genotype data from individuals of European ancestry to determine associations of common single nucleotide polymorphisms (SNPs) in 6 familial cerebral SVD genes (<i>COL4A1</i>, <i>COL4A2</i>, <i>NOTCH3</i>, <i>HTRA1</i>, <i>TREX1</i>, and <i>CECR1</i>) with intracerebral hemorrhage (ICH) (deep, lobar, all; 1,878 cases, 2,830 controls) and ischemic stroke (IS) (lacunar, cardioembolic, large vessel disease, all; 19,569 cases, 37,853 controls). We applied data quality filters and set statistical significance thresholds accounting for linkage disequilibrium and multiple testing.<h4>Results</h4>A locus in <i>COL4A2</i> 2017-01-01T00:00:00Z2017 Oct2026-04-29T09:03:41.108Z2019-03-27T00:03:40ZS-EPMC56643022895487810.1212/WNL.000000000000456010.1212/wnl.0000000000004560