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Genome-wide analyses reveal a potential role for the MAPT, MOBP, and APOE loci in sporadic frontotemporal dementia

Manzoni, Claudia (author)
UCL School of Pharmacy
Kia, Demis A. (author)
University College London
Ferrari, Raffaele (author)
University College London
show more...
Leonenko, Ganna (author)
Cardiff University
Costa, Beatrice (author)
University College London
Saba, Valentina (author)
University of Pavia
Jabbari, Edwin (author)
University College London
Tan, Manuela MX (author)
Oslo university hospital,University College London
Albani, Diego (author)
Mario Negri Institute for Pharmacological Research
Alvarez, Victoria (author)
Asturias General Hospital,Instituto de Investigación Sanitaria del Principado de Asturias (ISPA)
Alvarez, Ignacio (author)
Fundació Docència i Recerca MútuaTerrassa,Mutua De Terrassa Hospital
Andreassen, Ole A. (author)
Oslo university hospital,University of Oslo
Angiolillo, Antonella (author)
University of Molise
Arighi, Andrea (author)
Maggiore Hospital Policlinico
Baker, Matt (author)
Mayo Clinic Florida
Benussi, Luisa (author)
Centro San Giovanni di Dio Fatebenefratelli
Bessi, Valentina (author)
University of Florence
Binetti, Giuliano (author)
Centro San Giovanni di Dio Fatebenefratelli
Blackburn, Daniel J. (author)
University of Sheffield
Boada, Merce (author)
International University of Catalonia,CIBER Enfermedades Neurodegenerativas (CIBERNED)
Boeve, Bradley F. (author)
Mayo Clinic Minnesota
Borrego-Ecija, Sergi (author)
Hospital Clínic of Barcelona
Borroni, Barbara (author)
University of Brescia
Bråthen, Geir (author)
Norwegian University of Science and Technology,St. Olav’s University Hospital
Brooks, William S. (author)
University of New South Wales
Bruni, Amalia C. (author)
Regional Neurogenetic Centre, ASPCZ
Caroppo, Paola (author)
Carlo Besta Neurological Institute, IRCCS
Bandres-Ciga, Sara (author)
National Institute on Aging, United States
Clarimon, Jordi (author)
Autonomous University of Barcelona
Colao, Rosanna (author)
Regional Neurogenetic Centre, ASPCZ
Cruchaga, Carlos (author)
Washington University in St. Louis
Danek, Adrian (author)
University Hospital Munich
de Boer, Sterre CM (author)
University of Sydney,Vrije Universiteit Amsterdam
de Rojas, Itziar (author)
CIBER Enfermedades Neurodegenerativas (CIBERNED),International University of Catalonia
di Costanzo, Alfonso (author)
University of Molise
Dickson, Dennis W. (author)
Mayo Clinic Florida
Diehl-Schmid, Janine (author)
Inn-Salzach-Klinikum,Klinikum rechts der Isar
Dobson-Stone, Carol (author)
University of Sydney
Dols-Icardo, Oriol (author)
CIBER Enfermedades Neurodegenerativas (CIBERNED),Autonomous University of Barcelona
Donizetti, Aldo (author)
University of Naples Federico II
Dopper, Elise (author)
Erasmus University Medical Center
Durante, Elisabetta (author)
Azienda ULSS 2
Ferrari, Camilla (author)
University of Florence
Forloni, Gianluigi (author)
Mario Negri Institute for Pharmacological Research
Frangipane, Francesca (author)
Regional Neurogenetic Centre, ASPCZ
Fratiglioni, Laura (author)
Karolinska Institute,Karolinska University Hospital
Kramberger, Milica G. (author)
Karolinska Institute,University Medical Centre Ljubljana
Galimberti, Daniela (author)
Maggiore Hospital Policlinico,University of Milan
Gallucci, Maurizio (author)
Azienda ULSS 2
García-González, Pablo (author)
International University of Catalonia,CIBER Enfermedades Neurodegenerativas (CIBERNED)
Ghidoni, Roberta (author)
Centro San Giovanni di Dio Fatebenefratelli
Giaccone, Giorgio (author)
Carlo Besta Neurological Institute, IRCCS
Graff, Caroline (author)
Karolinska Institute,Karolinska University Hospital
Graff-Radford, Neill R. (author)
Mayo Clinic Florida
Grafman, Jordan (author)
Shirley Ryan AbilityLab
Halliday, Glenda M. (author)
University of Sydney
Hernandez, Dena G. (author)
National Institute on Aging, United States
Hjermind, Lena E. (author)
Copenhagen University Hospital
Hodges, John R. (author)
University of Sydney
Holloway, Guy (author)
University of Edinburgh
Huey, Edward D. (author)
Brown University
Illán-Gala, Ignacio (author)
CIBER Enfermedades Neurodegenerativas (CIBERNED),Autonomous University of Barcelona
Josephs, Keith A. (author)
Mayo Clinic Minnesota
Knopman, David S. (author)
Mayo Clinic Minnesota
Kristiansen, Mark (author)
Zayed Centre for Research into Rare Disease in Children,University College London
Kwok, John B. (author)
University of Sydney
Leber, Isabelle (author)
Assistance Publique des Hôpitaux de Paris,Paris-Sorbonne University
Leonard, Hampton L. (author)
National Institute on Aging, United States,German Center for Neurodegenerative Diseases (DZNE), Bonn,Data Tecnica International LLC
Libri, Ilenia (author)
University of Brescia
Lleo, Alberto (author)
CIBER Enfermedades Neurodegenerativas (CIBERNED),Autonomous University of Barcelona
Mackenzie, Ian R. (author)
Vancouver Coastal Health Research Institute,University of British Columbia
Madhan, Gaganjit K. (author)
Zayed Centre for Research into Rare Disease in Children,University College London
Maletta, Raffaele (author)
Regional Neurogenetic Centre, ASPCZ
Marquié, Marta (author)
International University of Catalonia,CIBER Enfermedades Neurodegenerativas (CIBERNED)
Maver, Ales (author)
University Medical Centre Ljubljana
Menendez-Gonzalez, Manuel (author)
University of Oviedo,Asturias General Hospital,Instituto de Investigación Sanitaria del Principado de Asturias (ISPA)
Milan, Graziella (author)
Geriatric Center “Frullone” ASL NA1
Miller, Bruce L. (author)
Trinity College Dublin,University of California, San Francisco
Morris, Christopher M. (author)
University of Newcastle upon Tyne
Morris, Huw R. (author)
University College London
Nacmias, Benedetta (author)
University of Florence,IRCCS Don Gnocchi Foundation
Newton, Judith (author)
University of Edinburgh
Nielsen, Jørgen E. (author)
Copenhagen University Hospital
Nilsson, Christer (author)
Lund University,Lunds universitet,Translationell Neurologi,Forskargrupper vid Lunds universitet,Restorative Parkinson Unit,Translational Neurology (TNY),Lund University Research Groups
Novelli, Valeria (author)
Centro Cardiologico Monzino
Padovani, Alessandro (author)
University of Brescia
Pal, Suvankar (author)
University of Edinburgh
Pasquier, Florence (author)
Lille University Hospital,National Institute for Health and Medical Research, France,University of Lille
Pastor, Pau (author)
Hospital Universitari Germans Trias i Pujol,Institute for Health Science Research Germans Trias i Pujol (IGTP)
Perneczky, Robert (author)
German Center for Neurodegenerative Diseases (DZNE), Bonn,University of Sheffield,Imperial College London,Munich Cluster for Systems Neurology,University Hospital Munich
Peterlin, Borut (author)
University Medical Centre Ljubljana
Petersen, Ronald C. (author)
Mayo Clinic Minnesota
Piguet, Olivier (author)
University of Sydney
Pijnenburg, Yolande AL (author)
Vrije Universiteit Amsterdam
Puca, Annibale A. (author)
IRCCS Multimedica,University of Salerno
Rademakers, Rosa (author)
University of Antwerp,Mayo Clinic Florida,Flanders Interuniversity Institute for Biotechnology
Rainero, Innocenzo (author)
Citta' della Salute e della Scienza Hospital-University of Turin,University of Turin
Reus, Lianne M. (author)
Vrije Universiteit Amsterdam,University of California, Los Angeles
Richardson, Anna MT (author)
University of Manchester
Riemenschneider, Matthias (author)
Saarland University Hospital
Rogaeva, Ekaterina (author)
Tanz Centre for Research in Neurodegenerative Diseases
Rogelj, Boris (author)
University of Ljubljana,Jožef Stefan Institute
Rollinson, Sara (author)
University of Manchester
Rosen, Howard (author)
University of California, San Francisco
Rossi, Giacomina (author)
Carlo Besta Neurological Institute, IRCCS
Rowe, James B. (author)
University of Cambridge
Rubino, Elisa (author)
Citta' della Salute e della Scienza Hospital-University of Turin,University of Turin
Ruiz, Agustin (author)
CIBER Enfermedades Neurodegenerativas (CIBERNED),International University of Catalonia
Salvi, Erika (author)
Carlo Besta Neurological Institute, IRCCS
Sanchez-Valle, Raquel (author)
Hospital Clínic of Barcelona
Sando, Sigrid Botne (author)
Norwegian University of Science and Technology,St. Olav’s University Hospital
Santillo, Alexander F. (author)
Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas
Saxon, Jennifer A. (author)
University of Manchester
Schlachetzki, Johannes CM (author)
University of California, San Diego
Scholz, Sonja W. (author)
National Institute of Neurological Disorders and Stroke (NINDS),Johns Hopkins University
Seelaar, Harro (author)
Erasmus University Medical Center
Seeley, William W. (author)
University of California, San Francisco
Serpente, Maria (author)
Maggiore Hospital Policlinico
Sorbi, Sandro (author)
University of Florence,IRCCS Don Gnocchi Foundation
Sordon, Sabrina (author)
Saarland University Hospital
St George-Hyslop, Peter (author)
Columbia University,Tanz Centre for Research in Neurodegenerative Diseases
Thompson, Jennifer C. (author)
University of Manchester
Van Broeckhoven, Christine (author)
Flanders Interuniversity Institute for Biotechnology,University of Antwerp
Van Deerlin, Vivianna M. (author)
University of Pennsylvania
Van der Lee, Sven J. (author)
Vrije Universiteit Amsterdam
Van Swieten, John (author)
Erasmus University Medical Center
Tagliavini, Fabrizio (author)
Carlo Besta Neurological Institute, IRCCS
van der Zee, Julie (author)
Flanders Interuniversity Institute for Biotechnology,University of Antwerp
Veronesi, Arianna (author)
Azienda ULSS 2
Vitale, Emilia (author)
CNR Istituto per le Tecnologie Applicate ai Beni Culturali (CNR-ITABC),Kean University
Waldo, Maria Landqvist (author)
Lund University,Lunds universitet,Kliniska Vetenskaper, Helsingborg,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Psykiatri, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Clinical Sciences, Helsingborg,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Psychiatry (Lund),Section IV,Department of Clinical Sciences, Lund
Yokoyama, Jennifer S. (author)
University of California, San Francisco,Trinity College Dublin
Nalls, Mike A. (author)
Data Tecnica International LLC,National Institute on Aging, United States
Momeni, Parastoo (author)
Rona Holdings
Singleton, Andrew B. (author)
National Institute on Aging, United States
Hardy, John (author)
Hong Kong University of Science and Technology,University College London,University College London Hospital,Reta Lila Weston Institute of Neurological Studies
Escott-Price, Valentina (author)
Cardiff University
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 (creator_code:org_t)
2024
2024
English 14 s.
In: American Journal of Human Genetics. - 0002-9297. ; 111:7, s. 1316-1329
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after Alzheimer disease (AD). Efforts in the field mainly focus on familial forms of disease (fFTDs), while studies of the genetic etiology of sporadic FTD (sFTD) have been less common. In the current work, we analyzed 4,685 sFTD cases and 15,308 controls looking for common genetic determinants for sFTD. We found a cluster of variants at the MAPT (rs199443; p = 2.5 × 10−12, OR = 1.27) and APOE (rs6857; p = 1.31 × 10−12, OR = 1.27) loci and a candidate locus on chromosome 3 (rs1009966; p = 2.41 × 10−8, OR = 1.16) in the intergenic region between RPSA and MOBP, contributing to increased risk for sFTD through effects on expression and/or splicing in brain cortex of functionally relevant in-cis genes at the MAPT and RPSA-MOBP loci. The association with the MAPT (H1c clade) and RPSA-MOBP loci may suggest common genetic pleiotropy across FTD and progressive supranuclear palsy (PSP) (MAPT and RPSA-MOBP loci) and across FTD, AD, Parkinson disease (PD), and cortico-basal degeneration (CBD) (MAPT locus). Our data also suggest population specificity of the risk signals, with MAPT and APOE loci associations mainly driven by Central/Nordic and Mediterranean Europeans, respectively. This study lays the foundations for future work aimed at further characterizing population-specific features of potential FTD-discriminant APOE haplotype(s) and the functional involvement and contribution of the MAPT H1c haplotype and RPSA-MOBP loci to pathogenesis of sporadic forms of FTD in brain cortex.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

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By the author/editor
Manzoni, Claudia
Kia, Demis A.
Ferrari, Raffael ...
Leonenko, Ganna
Costa, Beatrice
Saba, Valentina
show more...
Jabbari, Edwin
Tan, Manuela MX
Albani, Diego
Alvarez, Victori ...
Alvarez, Ignacio
Andreassen, Ole ...
Angiolillo, Anto ...
Arighi, Andrea
Baker, Matt
Benussi, Luisa
Bessi, Valentina
Binetti, Giulian ...
Blackburn, Danie ...
Boada, Merce
Boeve, Bradley F ...
Borrego-Ecija, S ...
Borroni, Barbara
Bråthen, Geir
Brooks, William ...
Bruni, Amalia C.
Caroppo, Paola
Bandres-Ciga, Sa ...
Clarimon, Jordi
Colao, Rosanna
Cruchaga, Carlos
Danek, Adrian
de Boer, Sterre ...
de Rojas, Itziar
di Costanzo, Alf ...
Dickson, Dennis ...
Diehl-Schmid, Ja ...
Dobson-Stone, Ca ...
Dols-Icardo, Ori ...
Donizetti, Aldo
Dopper, Elise
Durante, Elisabe ...
Ferrari, Camilla
Forloni, Gianlui ...
Frangipane, Fran ...
Fratiglioni, Lau ...
Kramberger, Mili ...
Galimberti, Dani ...
Gallucci, Mauriz ...
García-González, ...
Ghidoni, Roberta
Giaccone, Giorgi ...
Graff, Caroline
Graff-Radford, N ...
Grafman, Jordan
Halliday, Glenda ...
Hernandez, Dena ...
Hjermind, Lena E ...
Hodges, John R.
Holloway, Guy
Huey, Edward D.
Illán-Gala, Igna ...
Josephs, Keith A ...
Knopman, David S ...
Kristiansen, Mar ...
Kwok, John B.
Leber, Isabelle
Leonard, Hampton ...
Libri, Ilenia
Lleo, Alberto
Mackenzie, Ian R ...
Madhan, Gaganjit ...
Maletta, Raffael ...
Marquié, Marta
Maver, Ales
Menendez-Gonzale ...
Milan, Graziella
Miller, Bruce L.
Morris, Christop ...
Morris, Huw R.
Nacmias, Benedet ...
Newton, Judith
Nielsen, Jørgen ...
Nilsson, Christe ...
Novelli, Valeria
Padovani, Alessa ...
Pal, Suvankar
Pasquier, Floren ...
Pastor, Pau
Perneczky, Rober ...
Peterlin, Borut
Petersen, Ronald ...
Piguet, Olivier
Pijnenburg, Yola ...
Puca, Annibale A ...
Rademakers, Rosa
Rainero, Innocen ...
Reus, Lianne M.
Richardson, Anna ...
Riemenschneider, ...
Rogaeva, Ekateri ...
Rogelj, Boris
Rollinson, Sara
Rosen, Howard
Rossi, Giacomina
Rowe, James B.
Rubino, Elisa
Ruiz, Agustin
Salvi, Erika
Sanchez-Valle, R ...
Sando, Sigrid Bo ...
Santillo, Alexan ...
Saxon, Jennifer ...
Schlachetzki, Jo ...
Scholz, Sonja W.
Seelaar, Harro
Seeley, William ...
Serpente, Maria
Sorbi, Sandro
Sordon, Sabrina
St George-Hyslop ...
Thompson, Jennif ...
Van Broeckhoven, ...
Van Deerlin, Viv ...
Van der Lee, Sve ...
Van Swieten, Joh ...
Tagliavini, Fabr ...
van der Zee, Jul ...
Veronesi, Ariann ...
Vitale, Emilia
Waldo, Maria Lan ...
Yokoyama, Jennif ...
Nalls, Mike A.
Momeni, Parastoo
Singleton, Andre ...
Hardy, John
Escott-Price, Va ...
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MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Clinical Medicin ...
and Neurology
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American Journal ...
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Lund University

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