American journal of human genetics · 2024

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

СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди

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Manzoni Claudia, Kia Demis A, Ferrari Raffaele, Leonenko Ganna, Costa Beatrice, Saba Valentina, Jabbari Edwin, Tan Manuela Mx, Albani Diego, Alvarez Victoria, Alvarez Ignacio, Andreassen Ole A, Angiolillo Antonella, Arighi Andrea, Baker Matt, Benussi Luisa, Bessi Valentina, Binetti Giuliano, Blackburn Daniel J, Boada Merce, Boeve Bradley F, Borrego-Ecija Sergi, Borroni Barbara, Bråthen Geir, Brooks William S, Bruni Amalia C, Caroppo Paola, Bandres-Ciga Sara, Clarimon Jordi, Colao Rosanna, Cruchaga Carlos, Danek Adrian, de Boer Sterre Cm, de Rojas Itziar, di Costanzo Alfonso, Dickson Dennis W, Diehl-Schmid Janine, Dobson-Stone Carol, Dols-Icardo Oriol, Donizetti Aldo, Dopper Elise, Durante Elisabetta, Ferrari Camilla, Forloni Gianluigi, Frangipane Francesca, Fratiglioni Laura, Kramberger Milica G, Galimberti Daniela, Gallucci Maurizio, García-González Pablo, Ghidoni Roberta, Giaccone Giorgio, Graff Caroline, Graff-Radford Neill R, Grafman Jordan, Halliday Glenda M, Hernandez Dena G, Hjermind Lena E, Hodges John R, Holloway Guy, Huey Edward D, Illán-Gala Ignacio, Josephs Keith A, Knopman David S, Kristiansen Mark, Kwok John B, Leber Isabelle, Leonard Hampton L, Libri Ilenia, Lleo Alberto, Mackenzie Ian R, Madhan Gaganjit K, Maletta Raffaele, Marquié Marta, Maver Ales, Menendez-Gonzalez Manuel, Milan Graziella, Miller Bruce L, Morris Christopher M, Morris Huw R, Nacmias Benedetta, Newton Judith, Nielsen Jørgen E, Nilsson Christer, Novelli Valeria, Padovani Alessandro, Pal Suvankar, Pasquier Florence, Pastor Pau, Perneczky Robert, Peterlin Borut, Petersen Ronald C, Piguet Olivier, Pijnenburg Yolande Al, Puca Annibale A, Rademakers Rosa, Rainero Innocenzo, Reus Lianne M, Richardson Anna Mt, Riemenschneider Matthias, Rogaeva Ekaterina, Rogelj Boris, Rollinson Sara, Rosen Howard, Rossi Giacomina, Rowe James B, Rubino Elisa, Ruiz Agustin, Salvi Erika, Sanchez-Valle Raquel, Sando Sigrid Botne, Santillo Alexander F, Saxon Jennifer A, Schlachetzki Johannes Cm, Scholz Sonja W, Seelaar Harro, Seeley William W, Serpente Maria, Sorbi Sandro, Sordon Sabrina, St George-Hyslop Peter, Thompson Jennifer C, Van Broeckhoven Christine, Van Deerlin Vivianna M, Van der Lee Sven J, Van Swieten John, Tagliavini Fabrizio, van der Zee Julie, Veronesi Arianna, Vitale Emilia, Waldo Maria Landqvist, Yokoyama Jennifer S, Nalls Mike A, Momeni Parastoo, Singleton Andrew B, Hardy John, Escott-Price Valentina

Аннотация

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.

Предметные рубрики MeSH

Humans Frontotemporal Dementia tau Proteins Genome-Wide Association Study Apolipoproteins E Male Female Genetic Predisposition to Disease Aged Polymorphism, Single Nucleotide Genetic Loci Middle Aged Case-Control Studies Myelin Proteins

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

Ошибки и ограничения

Аннотация

Предметные рубрики MeSH