ArticleNature communications2025
Deciphering distinct genetic risk factors for FTLD-TDP pathological subtypes via whole-genome sequencing.
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Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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19citing papers in PubMed, 1 pooled it
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Consensus meta-analysis of genome-wide association studies for Alzheimer's disease and related dementias.Nature genetics · 2026Pooled it
- TDP-43 dysfunction induces cryptic circular RNAs in ALS/FTD.bioRxiv : the preprint server for biology · 2026Article
- A new era of genome-wide association studies in the field of Alzheimer's disease and overlapping co-pathologies: lessons learned from a neuropathology-centered approach.Acta neuropathologica · 2026Review
- TNIP1 As A Potential Factor In Neuronal Survival, Growth and Differentiation in the Cerebellar Cortex.Cerebellum (London, England) · 2026Article
- The UNC13A cryptic exon associates with cognitive impairment in Alzheimer's disease.Alzheimer's research & therapy · 2026Article
- Distinct proteomic CSF profiles in genetic frontotemporal lobar degeneration.Brain : a journal of neurology · 2026Article
- Pathology and Genetics in a Global Cohort of Parkinsonian Disorders.JAMA neurology · 2026Article
- Article
- Molecular dynamics of Brodmann Area 22 in development and autism.bioRxiv : the preprint server for biology · 2026Article
- Genetic analysis of neurodegenerative diseases.The Journal of clinical investigation · 2026Review
- A repeat expansion in GOLGA8A is a major risk factor for atypical frontotemporal lobar degeneration with ubiquitin-positive inclusions.Nature genetics · 2026Article
- The Genetics of TDP-43 Type C Neurodegeneration: A Whole-Genome Sequencing Study and Literature Review.Neurology. Genetics · 2026Article
- Pathology and genetics in a global cohort of Parkinsonian Disorders.medRxiv : the preprint server for health sciences · 2026Article
- Amyloid-linked versus age-driven copathologies in Alzheimer's dementia: differential associations withResearch square · 2026Article
- Expanding the spectrum of annexin A11 proteinopathy in frontotemporal lobar degeneration and motor neuron disease.Acta neuropathologica · 2025Article
- Disruption of Cell-Type-Specific Molecular Programs of Medium Spiny Neurons in Autism.bioRxiv : the preprint server for biology · 2025Article
- Consensus meta-analysis of genome-wide association studies for Alzheimer's disease and related dementia.medRxiv : the preprint server for health sciences · 2025Article
- Methylome analysis of FTLD patients with TDP-43 pathology identifies epigenetic signatures specific to pathological subtypes.Molecular neurodegeneration · 2025Article
- Analysis of the splicing landscape of the frontal cortex in FTLD-TDP reveals subtype specific patterns and cryptic splicing.Acta neuropathologica · 2025Article
Corrections and comments
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Authors and funding
119 authors.
Cyril PottierDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA. cpottier@wustl.edu.ORCID http://orcid.org/0000-0002-3049-9346
Fahri KüçükaliDepartment of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.ORCID http://orcid.org/0000-0002-3835-9639
Matt BakerDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.ORCID http://orcid.org/0009-0001-2691-5757
Anthony BatzlerDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
Gregory D JenkinsDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0001-6408-6227
Marka van BlitterswijkDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Cristina T VicenteDepartment of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.ORCID http://orcid.org/0000-0002-7882-9543
Wouter De CosterDepartment of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.ORCID http://orcid.org/0000-0002-5248-8197
Sarah WynantsDepartment of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
Pieter Van de WalleDepartment of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
Owen A RossDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.ORCID http://orcid.org/0000-0003-4813-756X
Melissa E MurrayDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.ORCID http://orcid.org/0000-0001-7379-2545
Júlia FauraDepartment of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
Stephen J HaggartyDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-7872-168X
Jeroen Gj van RooijDepartment of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0001-9754-073X
Merel O MolDepartment of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0003-2533-2530
Ging-Yuek R HsiungDepartment of Medicine, Division of Neurology, University of British Columbia, Vancouver, BC, Canada.ORCID http://orcid.org/0000-0002-8017-0856
Caroline GraffDivision of Neurogeriatrics, Karolinska Institutet, Solna, Sweden.
Linn ÖijerstedtDivision of Neurogeriatrics, Karolinska Institutet, Solna, Sweden.
Manuela NeumannGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Yan AsmannDepartment of Health Sciences Research, Mayo Clinic, Jacksonville, FL, USA.
Shannon K McDonnellDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0001-6201-369X
Saurabh BahetiDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0002-3564-7627
Keith A JosephsDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0003-2930-8634
Jennifer L WhitwellDepartment of Radiology, Mayo Clinic, Rochester, MN, USA.
Kevin F BieniekDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.ORCID http://orcid.org/0000-0003-4922-864X
Leah ForsbergDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0003-4086-9598
Hilary HeuerDepartment of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
Argentina Lario LagoDepartment of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
Ethan G GeierDepartment of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
Jennifer S YokoyamaDepartment of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-7274-2634
Alexis P OddiDepartment of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
Margaret FlanaganUniversity of Texas Health Science Center San Antonio, San Antonio, TX, USA.
Qinwen MaoDepartment of Pathology, University of Utah, Salt Lake City, UT, USA.
John R HodgesCentral Clinical School and Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia.
John B KwokUniversity of Sydney, Sydney, NSW, Australia.
Kimiko Domoto-ReillyDepartment of Neurology, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-7396-1633
Matthis SynofzikGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.ORCID http://orcid.org/0000-0002-2280-7273
Carlo WilkeGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Chiadi OnyikeDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
Bradford C DickersonDepartment of Neurology, Case Western Reserve University, Cleveland, OH, USA.ORCID http://orcid.org/0000-0002-5958-3445
Bret M EversDivision of Neuropathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0001-5686-0315
Brittany N DuggerDepartment of Pathology and Laboratory Medicine, University of California, Davis Medical Center, Sacramento, CA, USA.ORCID http://orcid.org/0000-0003-2141-8855
David G MunozSt. Michael's Hospital, Toronto, ON, Canada.
Julia KeithDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Lorne ZinmanSunnybrook Health Sciences Centre, Toronto, ON, Canada.
Ekaterina RogaevaKrembil Discovery Tower, Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-2852-0329
EunRan SuhDepartment of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Tamar GefenMesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University, Chicago, IL, USA.
Changiz GeulaMesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University, Chicago, IL, USA.
Sandra WeintraubMesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University, Chicago, IL, USA.ORCID http://orcid.org/0000-0003-2605-5205
Janine Diehl-SchmidDepartment of Psychiatry and Psychotherapy, Technical University of Munich, Munich, Germany.
Martin R FarlowDepartment of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID http://orcid.org/0000-0001-7897-5471
Dieter EdbauerGerman Center for Neurodegenerative Diseases (DZNE), Munich, Germany.ORCID http://orcid.org/0000-0002-7186-4653
Bryan K WoodruffDepartment of Neurology, Mayo Clinic, Scottsdale, AZ, USA.
Richard J CaselliDepartment of Neurology, Mayo Clinic, Scottsdale, AZ, USA.ORCID http://orcid.org/0000-0001-5784-2987
Laura L Donker KaatDepartment of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
Edward D HueyDepartment of Psychiatry and Human Behavior, Brown Alpert Medical School, Brown University, Providence, RI, USA.
Eric M ReimanBanner Alzheimer's Institute, Phoenix, AZ, USA.ORCID http://orcid.org/0000-0002-0705-3696
Simon MeadMRC Prion Unit at University College London, Institute of Prion Diseases, London, UK.ORCID http://orcid.org/0000-0002-4326-1468
Andrew KingDepartment of Basic and Clinical Neuroscience, London Neurodegenerative Diseases Brain Bank, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Sigrun RoeberCentre for Neuropathology and Prion Research, Ludwig-Maximilians-University of Munich, Munich, Germany.
Alissa L NanaDepartment of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-3474-8044
Nilufer Ertekin-TanerDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.ORCID http://orcid.org/0000-0003-4436-8889
David S KnopmanDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0002-6544-066X
Ronald C PetersenDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0002-8178-6601
Leonard PetrucelliDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Ryan J UittiDepartment of Neurology, Mayo Clinic, Jacksonville, FL, USA.
Zbigniew K WszolekDepartment of Neurology, Mayo Clinic, Jacksonville, FL, USA.ORCID http://orcid.org/0000-0001-5487-1053
Eliana Marisa RamosDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Lea T GrinbergDepartment of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-6809-0618
Maria Luisa Gorno TempiniDepartment of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
Howard J RosenDepartment of Pathology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
Salvatore SpinaDepartment of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-3570-9143
Olivier PiguetSchool of Psychology and Brain and Mind Centre, University of Sydney, Sydney, SWA, Australia.ORCID http://orcid.org/0000-0002-6696-1440
Murray GrossmanDepartment of Neurology, Penn Frontotemporal Degeneration Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
John Q TrojanowskiDepartment of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-9239-8794
C Dirk KeeneUniversity of Washington BioRepository and Integrated Neuropathology (BRaIN) lab, Harborview Medical Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-5291-1469
Lee-Way JinM.I.N.D. Institute Laboratory, University of California, Davis Medical Center, Sacramento, CA, USA.
Johannes PrudloGerman Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.
Daniel H GeschwindDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-2896-3450
Robert A RissmanAlzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, San Diego, CA, USA.
Carlos CruchagaDepartment of Psychiatry, Knight Alzheimer Disease Research Center, Washington University School of Medicine, Saint Louis, MO, USA.ORCID http://orcid.org/0000-0002-0276-2899
Bernardino GhettiDepartment of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID http://orcid.org/0000-0002-1842-8019
Glenda M HallidayUniversity of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0003-0422-8398
Thomas G BeachCivin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, AZ, USA.
Geidy E SerranoCivin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, AZ, USA.
Thomas ArzbergerCentre for Neuropathology and Prion Research, Ludwig-Maximilians-University of Munich, Munich, Germany.
Jochen HermsGerman Center for Neurodegenerative Diseases (DZNE), Munich, Germany.ORCID http://orcid.org/0000-0002-6201-1042
Adam L BoxerDepartment of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-1215-5064
Lawrence S HonigDepartment of Neurology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-9703-2265
Jean P VonsattelDepartment of Pathology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY, USA.
Oscar L LopezDepartment of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-8546-8256
Julia KoflerDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
Charles L WhiteDivision of Neuropathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0002-3870-2804
Marla GearingDepartment of Pathology and Laboratory Medicine and Department of Neurology, Emory University, Atlanta, GA, USA.
Jonathan GlassDepartment of Pathology and Laboratory Medicine and Department of Neurology, Emory University, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-3295-4971
Jonathan D RohrerDepartment of Neurodegenerative Disease, Dementia Research Centre, University College London, Queen Square Institute of Neurology, London, UK.
David J IrwinDepartment of Neurology, Penn Frontotemporal Degeneration Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-5599-5098
Edward B LeeDepartment of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-4589-1180
Vivianna Van DeerlinDepartment of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-7400-9097
Rudolph CastellaniDepartment of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Marsel M MesulamMesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University, Chicago, IL, USA.
Maria C TartagliaKrembil Discovery Tower, Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-5944-8497
Elizabeth C FingerDepartment of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
Claire TroakesDepartment of Basic and Clinical Neuroscience, London Neurodegenerative Diseases Brain Bank, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.ORCID http://orcid.org/0000-0002-1790-7376
Safa Al-SarrajDepartment of Basic and Clinical Neuroscience, London Neurodegenerative Diseases Brain Bank, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Clifton L DalgardDepartment of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-2025-8239
Bruce L MillerDepartment of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
Harro SeelaarDepartment of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0003-1989-7527
Neill R Graff-RadfordDepartment of Neurology, Mayo Clinic, Jacksonville, FL, USA.
Bradley F BoeveDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0002-4153-8187
Ian Ra MackenzieDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.ORCID http://orcid.org/0000-0003-3875-2972
John C van SwietenDepartment of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.
William W SeeleyDepartment of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-1410-2027
Kristel SleegersDepartment of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.ORCID http://orcid.org/0000-0002-0283-2332
Dennis W DicksonDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.ORCID http://orcid.org/0000-0001-7189-7917
Joanna M BiernackaDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0001-9350-4440
Rosa RademakersDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA. rosa.rademakers@uantwerpen.vib.be.ORCID http://orcid.org/0000-0002-4049-0863
Funding
Technology and Remote Assessment CoreU19AG063911 · NIA · MAYO CLINIC ROCHESTER · PI ADAM L. BOXER, Bradley F Boeve · 2019 to 2026
$120.9MNational Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8MVascular Structure and Function in Cognitive AgingP01AG003949 · NIA · YESHIVA UNIVERSITY · PI Richard B. LIPTON · 1985 to 2026
$73.9MEarly Onset AD Consortium - the LEAD Study (LEADS)U01AG057195 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI APOSTOLOVA, LIANA G, CARRILLO, MARIA C · 2018 to 2023
$70.3MTDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2MTHERAPEUTIC EFFECTS OF INTRA-NASAL INSULIN DETEMIRP50AG005136 · NIA · UNIVERSITY OF WASHINGTON · PI GRABOWSKI, THOMAS J. · 1985 to 2019
$57.2MResearch Education ComponentP30AG062422 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Katherine P Rankin · 2019 to 2026
$36.9MResearch Education ComponentP30AG062677 · NIA · MAYO CLINIC ROCHESTER · PI KEJAL KANTARCI · 2019 to 2026
$33.5MResearch Education ComponentP30AG066468 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI C. Elizabeth Shaaban · 2020 to 2026
$29.4MUniversity of Washington Alzheimer's Disease Research CenterP30AG066509 · NIA · UNIVERSITY OF WASHINGTON · PI Amanda D. Boyd · 2020 to 2026
$29.0MThe Goizueta Alzheimer's Disease Research CenterP30AG066511 · NIA · EMORY UNIVERSITY · PI ALLAN I LEVEY · 2020 to 2026
$29.0MNeuropathology CoreP30AG013854 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI VASSAR, ROBERT J · 1996 to 2020
$28.9MNIA NIH HHS P01 AG003949NIA NIH HHS P01 AG019724NIA NIH HHS P01 AG066597NIA NIH HHS P30 AG010129NIA NIH HHS P30 AG012300NIA NIH HHS P30 AG013854NIA NIH HHS P30 AG062422NIA NIH HHS P30 AG062677NIA NIH HHS P30 AG066468NIA NIH HHS P30 AG066509NIA NIH HHS P30 AG066511NIA NIH HHS P30 AG066530NIA NIH HHS P30 AG072972NIA NIH HHS P30 AG072977NIA NIH HHS P30 AG072979NIA NIH HHS P50 AG005136NIA NIH HHS P50 AG023501NIA NIH HHS R01 AG037491NIA NIH HHS R01 AG062268NIA NIH HHS R01 AG077444NIA NIH HHS R01 AG091388NIA NIH HHS U01 AG045390NIA NIH HHS U01 AG057195NIA NIH HHS U01 AG079850NIA NIH HHS U19 AG063911NIA NIH HHS U24 AG021886NIDCD NIH HHS R01 DC008552NIDCD NIH HHS R01 DC010367NIDCD NIH HHS R01 DC012519NIMH NIH HHS R01 MH120794NINDS NIH HHS P01 NS084974NINDS NIH HHS R01 NS085770NINDS NIH HHS R21 NS094684NINDS NIH HHS U54 NS092089NINDS NIH HHS UG3 NS103870U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) UG3/UH3 NS103870
Abstract
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 in distinct tissues, brain regions, and neuronal subtypes, suggesting distinct disease aetiologies in each of the subtypes. Rare variant analysis confirmed TBK1 and identified C3AR1, SMG8, VIPR1, RBPJL, L3MBTL1 and ANO9, as novel subtype-specific FTLD-TDP risk genes, further highlighting the role of innate and adaptive immunity and notch signaling pathway in FTLD-TDP, with potential diagnostic and novel therapeutic implications.
Indexed as
DNA-Binding ProteinsFrontotemporal Lobar DegenerationGenetic Predisposition to DiseaseAgedBrainCohort StudiesFemaleGenome-Wide Association StudyHumansMaleMiddle AgedNerve Tissue ProteinsProtein Serine-Threonine KinasesRisk FactorsWhole Genome SequencingDNA-Binding ProteinsNerve Tissue ProteinsProtein Serine-Threonine KinasesTARDBP protein, humanTBK1 protein, human
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