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

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 anal...

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Detalles Bibliográficos
Autores: Manzoni, Claudia|||0000-0001-5367-4023, Kia, Demis A., Ferrari, Raffaele, Leonenko, Ganna|||0000-0001-8025-661X, Costa, Beatrice, Saba, Valentina, Jabbari, Edwin|||0000-0001-6844-882X, Tan, Manuela|||0000-0001-5835-669X, Albani, Diego|||0000-0002-7050-6723, Alvarez, Victoria|||0000-0002-1916-2523, Alvarez, Ignacio|||0000-0002-8537-3935, Andreassen, Ole A.|||0000-0002-4461-3568, Angiolillo, Antonella|||0000-0002-0158-3039, Arighi, Andrea|||0000-0003-2865-3970, Baker, Matt, Benussi, Luisa|||0000-0003-2836-8141, Bessi, Valentina|||0000-0002-6176-3584, Binetti, Giuliano|||0000-0003-2759-5844, Blackburn, Daniel J., Boada, Mercè|||0000-0003-2617-3009, Boeve, Bradley, Borrego-Écija, Sergi|||0000-0003-2557-0010, Borroni, Barbara|||0000-0001-9340-9814, Bråthen, Geir|||0000-0003-3224-7983, Brooks, William S., Bruni, Amalia|||0000-0003-3471-3343, Caroppo, Paola, Bandres-Ciga, Sara|||0000-0003-0056-1361, Clarimón, Jordi|||0000-0002-6824-6942, Colao, Rosanna, Cruchaga, Carlos|||0000-0002-0276-2899, Danek, Adrian|||0000-0001-8857-5383, de Boer, Sterre C., De Rojas, Itziar|||0000-0002-2148-381X, di Costanzo, Alfonso, Dickson, Dennis W.|||0000-0001-7189-7917, Diehl-Schmid, Janine|||0000-0002-7745-1382, Dobson-Stone, Carol, Dols Icardo, Oriol|||0000-0003-2656-8748, Donizetti, Aldo, Dopper, Elise, Durante, Elisabetta, Ferrari, Camilla, Forloni, Gianluigi, Frangipane, Francesca, Fratiglioni, Laura, Kramberger, Milica G., Galimberti, Daniela|||0000-0002-9284-5953, Gallucci, Maurizio, García-González, Pablo|||0000-0003-0125-5403, Ghidoni, Roberta|||0000-0002-7691-1957, Giaccone, Giorgio|||0000-0002-4803-0802, Graff, Caroline|||0000-0002-9949-2951, Graff-Radford, Neill R., Grafman, Jordan, Halliday, Glenda M., Hernandez, Dena G.|||0000-0002-0188-9927, Hjermind, Lena E., Hodges, John R., Holloway, Guy, Huey, Edward D., Illán-Gala, Ignacio|||0000-0002-5418-2052, Josephs, Keith A., Knopman, David S., Kristiansen, Mark, Kwok, John B., Leber, Isabelle, Leonard, Hampton L.|||0000-0003-2390-8110, Libri, Ilenia, Lleó, Alberto|||0000-0002-2568-5478, Mackenzie, Ian R., Madhan, Gaganjit K., Maletta, Raffaele|||0000-0002-0758-1835, Marquié, Marta|||0000-0002-0660-0950, Maver, Ales, Menéndez González, Manuel, Milan, Graziella, Miller, Bruce L.|||0000-0002-2152-4220, Morris, Christopher M., Morris, Huw|||0000-0002-5473-3774, Nacmias, Benedetta|||0000-0001-9338-9040, Newton, Judith, Nielsen, Jørgen E., Nilsson, Christer, Novelli, Valeria, Padovani, Alessandro|||0000-0002-0119-3639, Pal, Suvankar, Pasquier, Florence|||0000-0001-9880-9788, Pastor, Pau|||0000-0002-7493-8777, Perneczky, Robert|||0000-0003-1981-7435, Peterlin, Borut|||0000-0001-7824-4978, Petersen, Ronald C., Piguet, Olivier, Pijnenburg, Yolande AL., Puca, Annibale A., Rademakers, Rosa, Rainero, Innocenzo|||0000-0001-6074-9628, Reus, Lianne|||0000-0001-6936-242X, Richardson, Anna MT., Riemenschneider, Matthias, Rogaeva, Ekaterina, Rogelj, Boris|||0000-0003-3898-1943, Rollinson, Sara|||0000-0002-0921-4318, Rosen, Howard, Rossi, Giacomina|||0000-0001-6680-2725, Rowe, James B., Rubino, Elisa|||0000-0002-7553-7553, Ruiz Laza, Agustín|||0000-0003-2633-2495, Salvi, Erika|||0000-0002-2724-2291, Sanchez-Valle, Raquel|||0000-0001-7750-896X, Sando, Sigrid Botne, Santillo, Alexander F., Saxon, Jennifer A., Schlachetzki, Johannes CM., Scholz, Sonja|||0000-0002-6623-0429, Seelaar, Harro|||0000-0003-1989-7527, Seeley, William W., Serpente, Maria, Sorbi, Sandro|||0000-0002-0380-6670, Sordon, Sabrina, St George-Hyslop, Peter, Thompson, Jennifer C., Van Broeckhoven, Christine|||0000-0003-0183-7665, Van Deerlin, Vivianna|||0000-0002-7400-9097, van der Lee, Sven J.|||0000-0003-1606-8643, van Swieten, John, Tagliavini, Fabrizio|||0000-0003-1039-7315, Van der Zee, Julie|||0000-0003-4381-8040, Veronesi, Arianna, Vitale, Emilia|||0000-0003-4651-3875, Waldo, Maria Landqvist, Yokoyama, Jennifer S.|||0000-0001-7274-2634, Nalls, Mike A., Momeni, Parastoo, Singleton, Andrew B.|||0000-0001-5606-700X, Hardy, John|||0000-0002-3122-0423, Escott-Price, Valentina|||0000-0003-1784-5483
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:299705
Acceso en línea:https://ddd.uab.cat/record/299705
https://dx.doi.org/urn:doi:10.1016/j.ajhg.2024.05.017
Access Level:acceso abierto
Palabra clave:Aged
Apolipoproteins E
Case-Control Studies
Female
Frontotemporal Dementia
Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Male
Middle Aged
Myelin Proteins
Polymorphism, Single Nucleotide
Tau Proteins
Descripción
Sumario: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, OR = 1.27) and APOE (rs6857; p = 1.31 × 10, OR = 1.27) loci and a candidate locus on chromosome 3 (rs1009966; p = 2.41 × 10, 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.

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