C9orf72, age at onset, and ancestry help discriminate behavioral from language variants in FTLD cohorts.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Costa Beatrice, Manzoni Claudia, Bernal-Quiros Manuel, Kia Demis A, Aguilar Miquel, Alvarez Ignacio, Alvarez Victoria, Andreassen Ole, Anfossi Maria, Bagnoli Silvia, Benussi Luisa, Bernardi Livia, Binetti Giuliano, Blackburn Daniel, Boada Mercè, Borroni Barbara, Bowns Lucy, Bråthen Geir, Bruni Amalia C, Chiang Huei-Hsin, Clarimon Jordi, Colville Shuna, Conidi Maria E, Cope Tom E, Cruchaga Carlos, Cupidi Chiara, Di Battista Maria Elena, Diehl-Schmid Janine, Diez-Fairen Monica, Dols-Icardo Oriol, Durante Elisabetta, Flisar Dušan, Frangipane Francesca, Galimberti Daniela, Gallo Maura, Gallucci Maurizio, Ghidoni Roberta, Graff Caroline, Grafman Jordan H, Grossman Murray, Hardy John, Hernández Isabel, Holloway Guy J T, Huey Edward D, Illán-Gala Ignacio, Karydas Anna, Khoshnood Behzad, Kramberger Milica G, Kristiansen Mark, Lewis Patrick A, Lleó Alberto, Madhan Gaganjit K, Maletta Raffaele, Maver Aleš, Menendez-Gonzalez Manuel, Milan Graziella, Miller Bruce, Mol Merel O, Momeni Parastoo, Moreno-Grau Sonia, Morris Chris M, Nacmias Benedetta, Nilsson Christer, Novelli Valeria, Öijerstedt Linn, Padovani Alessandro, Pal Suvankar, Panchbhaya Yasmin, Pastor Pau, Peterlin Borut, Piaceri Irene, Pickering-Brown Stuart, Pijnenburg Yolande A L, Puca Annibale A, Rainero Innocenzo, Rendina Antonella, Richardson Anna M T, Rogaeva Ekaterina, Rogelj Boris, Rollinson Sara, Rossi Giacomina, Rossmeier Carola, Rowe James B, Rubino Elisa, Ruiz Agustín, Sanchez-Valle Raquel, Sando Sigrid B, Santillo Alexander F, Saxon Jennifer, Scarpini Elio, Serpente Maria, Smirne Nicoletta, Sorbi Sandro, Suh EunRan, Tagliavini Fabrizio, Thompson Jennifer C, Trojanowski John Q, Van Deerlin Vivianna M, Van der Zee Julie, Van Broeckhoven Christine, van Rooij Jeroen, Van Swieten John C, Veronesi Arianna, Vitale Emilia, Waldö Maria L, Woodward Cathy, Yokoyama Jennifer, Escott-Price Valentina, Polke James M, Ferrari Raffaele, International FTD-Genetics Consortium
Аннотация
METHODS: We evaluated expansions frequency in the entire cohort (n = 1,396; behavioral variant frontotemporal dementia [bvFTD] [n = 800], primary progressive aphasia [PPA] [n = 495], and FTLD-motor neuron disease [MND] [n = 101]). We then focused on the bvFTD and PPA cases and tested for association between expansion status, syndromes, genetic ancestry, and AAO applying statistical tests comprising Fisher exact tests, analysis of variance with Tukey post hoc tests, and logistic and nonlinear mixed-effects model regressions.
RESULTS: We found C9orf72 pathogenic expansions in 4% of all cases (56/1,396). Expansion carriers differently distributed across syndromes: 12/101 FTLD-MND (11.9%), 40/800 bvFTD (5%), and 4/495 PPA (0.8%). While addressing population substructure through principal components analysis (PCA), we defined 2 patients groups with Central/Northern (n = 873) and Southern European (n = 523) ancestry. The proportion of expansion carriers was significantly higher in bvFTD compared to PPA (5% vs 0.8% [p = 2.17 × 10-5; odds ratio (OR) 6.4; confidence interval (CI) 2.31-24.99]), as well as in individuals with Central/Northern European compared to Southern European ancestry (4.4% vs 1.8% [p = 1.1 × 10-2; OR 2.5; CI 1.17-5.99]). Pathogenic expansions and Central/Northern European ancestry independently and inversely correlated with AAO. Our prediction model (based on expansions status, genetic ancestry, and AAO) predicted a diagnosis of bvFTD with 64% accuracy.
CONCLUSIONS: Our results indicate correlation between pathogenic C9orf72 expansions, AAO, PCA-based Central/Northern European ancestry, and a diagnosis of bvFTD, implying complex genetic risk architectures differently underpinning the behavioral and language variant syndromes.