biostudies-literaturePottier CConsortium for Frontotemporal dementiaGerman Research FoundationTelethon FoundationGamla TjänarinnorNIA NIH HHSTexas Tech University Health Sciences CenterAIRAlzh onlus – ANCC-COOPNational Institutes of HealthThe Tau Consortium and the Consortium for Frontotemporal Dementia ResesarchNational Institute on AgingHarry T Mangurian Jr Lewy Body Dementia ProgramMinistry of Health, Medical University of GdanskNIDCD NIH HHSBrain Foundation SwedenNational Institute for Health Research (NIHR)McCune FoundationNINDS NIH HHSFondazione Cassa di Risparmio di FirenzeNovo Nordisk FondenStohnes FoundationNHMRCMemorabel 2013 Presympt FTDPHRC FTLDexomeNIHR Queen Square Dementia Biomedical Research UnitLundbeck FoundationElse Kröner Fresenius StiftungNINDSInvestissements d&apos;avenirMRC Centre on Parkinson&apos;sArizona Biomedical Research CommissionAlzheimer Foundation SwedenMinistry of Health FinalizzataNomis FoundationBluefield Project to Cure FTDMedical Research CouncilLC Campbell FoundationJPND RiModAustralian Research Council Centre of Excellence in Cognition and its DisordersUniversity of Pittsburgh Brain InstituteWellcome TrustStockholm County CouncilCarl B and Florence E King FoundationItalian Ministry of HealthSwedish Brain PowerWolfson FoundationGerman Helmholtz AssociationSwedish FTD InitiativeSwedish Research CouncilAlzheimer&apos;s SocietyDepartment of Veterans AffairsAustralian National Health and Medical Research CouncilLittle Family FoundationMRC Clinician ScientistAlzheimer&apos;s Research UKWinspear Family Center for Research on the Neuropathology of Alzheimer DiseaseFundació Marató de TV3, Barcelona, SpainBrain Research TrustArizona Department of Health ServicesNIHR Rare Disease Translational ResearchSydney Research Excellence InitiativeBLRD VAGHR FoundationNIH/National Institute of Neurological Disorders and StrokeMayo Clinic DorothyAlzheimer NederlandNeuroSleep Centre of Research ExcellenceLeonard Wolfson Experimental Neurology Centre Clinical Research FacilityNational Institute on Deafness and Other Communication DisordersCanadian Consortium on Neurodegeneration in AgingGerman Federal Ministry of Education and ResearchNational Health and Medical Research Council of AustraliaSun Health FoundationMichael J Fox Foundation for Parkinson&apos;s ResearchMayo Clinic FoundationKarolinska InstitutetAlzheimer's SocietyNIHR UCLH Biomedical Research CentreDementia Foundation Sweden548-558https://www.ebi.ac.uk/biostudies/studies/S-EPMC6237181biostudies-literatureUnknown17(6)<h4>Background</h4>Loss-of-function mutations in GRN cause frontotemporal lobar degeneration (FTLD). Patients with GRN mutations present with a uniform subtype of TAR DNA-binding protein 43 (TDP-43) pathology at autopsy (FTLD-TDP type A); however, age at onset and clinical presentation are variable, even within families. We aimed to identify potential genetic modifiers of disease onset and disease risk in GRN mutation carriers.<h4>Methods</h4>The study was done in three stages: a discovery stage, a replication stage, and a meta-analysis of the discovery and replication data. In the discovery stage, genome-wide logistic and linear regression analyses were done to test the association of genetic variants with disease risk (case or control status) and age at onset in patients with a GRN mutatThe Lancet. NeurologyPotential genetic modifiers of disease risk and age at onset in patients with frontotemporal lobar degeneration and GRN mutations: a genome-wide association study.PMC6237181CL-2012-18-010RO1 AG041797U54 NS092089U01 AG046139WE.15-2014-08FTLDc O1GI1007AP30 AG019610R01 AG051848NNF16OC0020984UO1 AG00678613779420143810P30 AG10124P50 AG008702P30 AG010124CE110001021R248-2017-431P30 AG012300NNF11OC10145142015-029266304341079679P30 AG062429284RF1 AG053303R01 AG05060310377461037747MR/L016397/10011R01 AG037491I01 BX003040R21 AG051839R01 NS080820211002BRC149/NS/MHP01 AG003991MC_UU_00024/1RF1 AG044546P30 AG010133MR/J009482/1P01 NS084974P01 AG019724U01 AG006786P50 AG005681P30 NS055077P01 AG017586R35 NS0972611060992U24 NS072026U24 AG021886R01 AG044546R01 AG041797P50 AG08702P50 AG02350105-901R01 DC008552P30 AG013854APP11032581001 (TGB)MR/M023664/1529-2014-7504R90-2011-77237330510244001P50 AG025688P50 NS072187P50 AG005131RF AG0515041062539NF-SI-0617-10175RF1 AG051504P50 AG005133R248-2016-25181095127R01 NS076837U24 NS095871ANR-10-IAIHU-06P50 AG016574MR/M008525/1521-2010-3134G0701441U01 AG045390P01 AG02627670-73305-98-105Antonell ARossi GJenkins GDSuh EBrooks WSBagnoli SLlado AHodges JRNeumann MSpina SFinger ECIrwin DJGhidoni RKofler JBorroni BFinch NAFumagalli GGPetrucelli LKwok JBRogaeva EGallo MGhetti BWhite CLGrafman JBieniek KFCruchaga CAnfossi MChristopher EGrossman MPadovani AGlass JWilke Cvan Rooij JGJMaletta RLee EBSeeley WWScarpini EOblak ACairns NJMoreno FVan Deerlin VMRen YPiguet ONacmias BMurell JRPasquier FHuey EDBenussi LRichardson AFerrari CMomeni PSlawek JBoeve BFWeintraub SFrangipane FMurray MEGrinberg LTKnopman DSBlack SETroakes CMead SZhou XSitek EGraff CZulaica MBaker MParsons TMMann DBeach TGGalimberti DDickson DWHannequin DPickering-Brown SRademakers RLopez OLTrojanowski JQOijerstedt LMesulam MMLe Ber IGraff-Radford NRPerkerson RBCaselli RJWszolek ZKvan Swieten JCSynofzik MBiernacka JMReiman EMDiehl-Schmid JSerie DJRollinson SLopez de Munain AJosephs KAFerrari RRohrer JDHeutink PWong THNielsen JEDeJesus-Hernandez MSeelaar HMasellis MPetersen RCSnowden JSorbi SKjolby MPottier CBruni ACErtekin-Taner NHalliday GMMiller BLHsiung GRWinkelmann JAl-Sarraj SHardy JPiaceri IBigio EHVonsattel JPvan Blitterswijk MKarydas AMNykjaer AParisi JEGearing MTagliavini FHonig LSJohannsen PGeula CRissman RABoxer ALNoel Sabbagh MLippa CFMackenzie IRABinetti GEvers BMSanchez-Valle RfalsePotential genetic modifiers of disease risk and age at onset in patients with frontotemporal lobar degeneration and GRN mutations: a genome-wide association study.<h4>Background</h4>Loss-of-function mutations in GRN cause frontotemporal lobar degeneration (FTLD). Patients with GRN mutations present with a uniform subtype of TAR DNA-binding protein 43 (TDP-43) pathology at autopsy (FTLD-TDP type A); however, age at onset and clinical presentation are variable, even within families. We aimed to identify potential genetic modifiers of disease onset and disease risk in GRN mutation carriers.<h4>Methods</h4>The study was done in three stages: a discovery stage, a replication stage, and a meta-analysis of the discovery and replication data. In the discovery stage, genome-wide logistic and linear regression analyses were done to test the association of genetic variants with disease risk (case or control status) and age at onset in patients with a GRN mutat2018-01-01T00:00:00Z2018 Jun2026-05-06T05:36:56.642Z2026-04-07T22:12:29.833ZS-EPMC62371812972459210.1016/s1474-4422(18)30126-110.1016/S1474-4422(18)30126-1