@article{eprints2875,
         journal = {The Lancet Neurology},
       publisher = {Elsevier},
          author = {Raffaele Ferrari and Dena G Hernandez and Michael A Nalls and Jonathan D Rohrer and Adaikalavan Ramasamy and John B J Kwok and Carol Dobson-Stone and William S Brooks and Peter R Schofield and Glenda M Halliday and John R Hodges and Olivier Piguet and Lauren Bartley and Elizabeth Thompson and Eric Haan and Isabel Hern{\'a}ndez and Agust{\'i}n Ruiz and Merc{\`e} Boada and Barbara Borroni and Alessandro Padovani and Carlos Cruchaga and Nigel J Cairns and Luisa Benussi and Giuliano Binetti and Roberta Ghidoni and Gianluigi Forloni and Daniela Galimberti and Chiara Fenoglio and Maria Serpente and Elio Scarpini and Jordi Clarim{\'o}n and Alberto Lle{\'o} and Rafael Blesa and Maria Landqvist Wald{\"o} and Karin Nilsson and Christer Nilsson and Ian R A Mackenzie and Ging-Yuek R Hsiung and David M A Mann and Jordan Grafman and Christopher M Morris and Johannes Attems and Timothy D Griffiths and Ian G McKeith and Alan J Thomas and Pietro Pietrini and Edward D Huey and Eric M. Wassermann and Atik Baborie and Evelyn Jaros and Michael C. Tierney and Pau Pastor and Cristina Razquin and Sara Ortega-Cubero and Elena Alonso and Robert Perneczky and Janine Diehl-Schmid and Panagiotis Alexopoulos and Alexander Kurz and Innocenzo Rainero and Elisa Rubino and Lorenzo Pinessi and Ekaterina Rogaeva and Peter St George-Hyslop and Giacomina Rossi and Fabrizio Tagliavini and Giorgio Giaccone and James B Rowe and Johannes C M Schlachetzki and James Uphill and John Collinge and Simon Mead and Adrian Danek and Vivianna M Van Deerlin and Murray Grossman and John Q Trojanowski and Julie van der Zee and William Deschamps and Tim Van Langenhove and Marc Cruts and Christine Van Broeckhoven and Stefano F Cappa and Isabelle Le Ber and Didier Hannequin and V{\'e}ronique Golfier and Martine Vercelletto and Alexis Brice and Benedetta Nacmias and Sandro Sorbi and Silvia Bagnoli and Irene Piaceri and J{\o}rgen E Nielsen and Lena E Hjermind and Matthias Riemenschneider and Manuel Mayhaus and Bernd Ibach and Gilles Gasparoni and Sabrina Pichler and Wei Gu and Martin N Rossor and Nick C Fox and Jason D Warren and Maria Grazia Spillantini and Huw R Morris and Patrizia Rizzu and Peter Heutink and Julie S Snowden and Sara Rollinson and Anna Richardson and Alexander Gerhard and Amalia C Bruni and Raffaele Maletta and Francesca Frangipane and Chiara Cupidi and Livia Bernardi and Maria Anfossi and Maura Gallo and Maria Elena Conidi and Nicoletta Smirne and Rosa Rademakers and Matt Baker and Dennis W Dickson and Neill R. Graff-Radford and Ronald C Petersen and David Knopman and Keith A Josephs and Bradley F Boeve and Joseph E Parisi and William W Seeley and Bruce L Miller and Anna M Karydas and Howard Rosen and John C van Swieten and Elise G P Dopper and Harro Seelaar and Yolande A L Pijnenburg and Philip Scheltens and Giancarlo Logroscino and Rosa Capozzo and Valeria Novelli and Annibale A Puca and Massimo Franceschi and Alfredo Postiglione and Graziella Milan and Paolo Sorrentino and Mark Kristiansen and Huei-Hsin Chiang and Caroline Graff and Florence Pasquier and Adeline Rollin and Vincent Deramecourt and Florence Lebert and Dimitrios Kapogiannis and Luigi Ferrucci and Stuart Pickering-Brown and Andrew B Singleton and John Hardy and Parastoo Momeni},
           title = {Frontotemporal dementia and its subtypes: a genome-wide association study},
            year = {2014},
          volume = {13},
           pages = {686 -- 699},
          number = {7},
        abstract = {SummaryBackground Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes{--}MAPT, GRN, and C9orf72{--}have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder. Methods We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with \{FTD\} and 9402 healthy controls. To reduce genetic heterogeneity, all participants were of European ancestry. In the discovery phase (samples from 2154 patients with \{FTD\} and 4308 controls), we did separate association analyses for each \{FTD\} subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and \{FTD\} overlapping with motor neuron disease FTD-MND), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p\<5 {$\times$} 10?8) single-nucleotide polymorphisms. Findings We identified novel associations exceeding the genome-wide significance threshold (p\<5 {$\times$} 10?8). Combined (joint) analyses of discovery and replication phases showed genome-wide significant association at 6p21.3, {$\backslash$}\{HLA{$\backslash$}\} locus (immune system), for rs9268877 (p=1?05 {$\times$} 10?8; odds ratio=1?204 95\% {$\backslash$}\{CI{$\backslash$}\} 1?11?1?30), rs9268856 (p=5?51 {$\times$} 10?9; 0?809 0?76?0?86) and rs1980493 (p value=1?57 {$\times$} 10?8, 0?775 0?69?0?86) in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38/CTSC (the transcripts of which are related to lysosomal biology), for the behavioural {$\backslash$}\{FTD{$\backslash$}\} subtype for which joint analyses showed suggestive association for rs302668 (p=2?44 {$\times$} 10?7; 0?814 0?71?0?92). Analysis of expression and methylation quantitative trait loci data suggested that these loci might affect expression and methylation in cis. Interpretation Our findings suggest that immune system processes (link to 6p21.3) and possibly lysosomal and autophagy pathways (link to 11q14) are potentially involved in FTD. Our findings need to be replicated to better define the association of the newly identified loci with disease and to shed light on the pathomechanisms contributing to FTD. Funding The National Institute of Neurological Disorders and Stroke and National Institute on Aging, the Wellcome/MRC Centre on Parkinson's disease, Alzheimer's Research UK, and Texas Tech University Health Sciences Center.},
             url = {http://eprints.imtlucca.it/2875/}
}