biostudies-literaturePottier CU.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and StrokeNIA NIH HHSNIDCD NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)NINDS NIH HHS3914https://www.ebi.ac.uk/biostudies/studies/S-EPMC12032271biostudies-literatureUnknown16(1)Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) is a fatal neurodegenerative disorder with only a limited number of risk loci identified. We report our comprehensive genome-wide association study as part of the International FTLD-TDP Whole-Genome Sequencing Consortium, including 985 patients and 3,153 controls compiled from 26 institutions/brain banks in North America, Europe and Australia, and meta-analysis with the Dementia-seq cohort. We confirm UNC13A as the strongest overall FTLD-TDP risk factor and identify TNIP1 as a novel FTLD-TDP risk factor. In subgroup analyzes, we further identify genome-wide significant loci specific to each of the three main FTLD-TDP pathological subtypes (A, B and C), as well as enrichment of risk loci Nature communicationsDeciphering distinct genetic risk factors for FTLD-TDP pathological subtypes via whole-genome sequencing.PMC12032271R01 AG077444U01 AG057195P30 AG062677P01 NS084974P01 AG019724U54 NS092089R01 NS085770U24 AG021886P30 AG072972P30 AG066468R01 DC010367R01 DC008552P30 AG010129P30 AG072979P30 AG013854U19 AG063911P30 AG012300P50 AG005136P30 AG062422R21 NS094684P01 AG003949UG3/UH3 NS103870P30 AG066509R01 AG091388R01 DC012519UG3 NS103870U01 AG045390P30 AG066511R01 AG037491U01 AG079850P01 AG066597Jenkins GDFlanagan MSuh EHodges JRNeumann MKucukali FSpina SMunoz DGRosen HJVan Deerlin VFinger ECOnyike CIrwin DJVan de Walle PKofler JCastellani RJin LWZinman LPetrucelli LKwok JBRogaeva EWynants SNana ALDalgard CLMol MOGhetti BWhite CLBieniek KFCruchaga CGrossman MUitti RJGlass JHeuer HWilke CTartaglia MCLee EBForsberg LSeeley WWPiguet OLago ALHuey EDWhitwell JLHerms JBoeve BFWeintraub SMurray MEGrinberg LTDe Coster WKnopman DSVicente CTTroakes CMead SArzberger TMcDonnell SKBatzler AGraff CBaker MMackenzie IRvan Rooij JGBeach TGAsmann YKeene CDTempini MLGDickson DWBaheti SFarlow MRKeith JRademakers ROijerstedt LRamos EMTrojanowski JQLopez OLMesulam MMGraff-Radford NRCaselli RJWszolek ZKGeier EGvan Swieten JCDomoto-Reilly KSynofzik MBiernacka JMDiehl-Schmid JReiman EMPrudlo JJosephs KARohrer JDSeelaar HDickerson BCPetersen RCFaura JOddi APEdbauer DRoeber SPottier CErtekin-Taner NHalliday GMMiller BLSleegers KHsiung GRAl-Sarraj SGefen TMao QVonsattel JPvan Blitterswijk MHaggarty SJDonker Kaat LLDugger BNGearing MHonig LSGeula CRissman RABoxer ALGeschwind DHRoss OAYokoyama JSSerrano GEKing AEvers BMWoodruff BKfalseDeciphering distinct genetic risk factors for FTLD-TDP pathological subtypes via whole-genome sequencing.Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) is a fatal neurodegenerative disorder with only a limited number of risk loci identified. We report our comprehensive genome-wide association study as part of the International FTLD-TDP Whole-Genome Sequencing Consortium, including 985 patients and 3,153 controls compiled from 26 institutions/brain banks in North America, Europe and Australia, and meta-analysis with the Dementia-seq cohort. We confirm UNC13A as the strongest overall FTLD-TDP risk factor and identify TNIP1 as a novel FTLD-TDP risk factor. In subgroup analyzes, we further identify genome-wide significant loci specific to each of the three main FTLD-TDP pathological subtypes (A, B and C), as well as enrichment of risk loci 2025-01-01T00:00:00Z2025 Apr2026-06-01T20:10:16.652Z2025-07-03T03:04:34.136ZS-EPMC120322714028097610.1038/s41467-025-59216-0