{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:49:02Z","timestamp":1790434142381,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The G4C2-repeat expansion in C9orf72 is the most common cause of frontotemporal dementia and of amyotrophic lateral sclerosis. The variability of age at onset and phenotypic presentations is a hallmark of C9orf72 disease. In this study, we aimed to identify modifying factors of disease onset in C9orf72 carriers using a family-based approach, in pairs of C9orf72 carrier relatives with concordant or discordant age at onset. Linkage and association analyses provided converging evidence for a locus on chromosome Xq27.3. The minor allele A of rs1009776 was associated with an earlier onset (P\u2009=\u20091 \u00d7 10\u22125). The association with onset of dementia was replicated in an independent cohort of unrelated C9orf72 patients (P\u2009=\u20090.009). The protective major allele delayed the onset of dementia from 5 to 13\u2009years on average depending on the cohort considered. The same trend was observed in an independent cohort of C9orf72 patients with extreme deviation of the age at onset (P\u2009=\u20090.055). No association of rs1009776 was detected in GRN patients, suggesting that the effect of rs1009776 was restricted to the onset of dementia due to C9orf72. The minor allele A is associated with a higher SLITRK2 expression based on both expression quantitative trait loci (eQTL) databases and in-house expression studies performed on C9orf72 brain tissues. SLITRK2 encodes for a post-synaptic adhesion protein. We further show that synaptic vesicle glycoprotein 2 and synaptophysin, two synaptic vesicle proteins, were decreased in frontal cortex of C9orf72 patients carrying the minor allele. Upregulation of SLITRK2 might be associated with synaptic dysfunctions and drives adverse effects in C9orf72 patients that could be modulated in those carrying the protective allele. How the modulation of SLITRK2 expression affects synaptic functions and influences the disease onset of dementia in C9orf72 carriers will require further investigations. In summary, this study describes an original approach to detect modifier genes in rare diseases and reinforces rising links between C9orf72 and synaptic dysfunctions that might directly influence the occurrence of first symptoms.<\/jats:p>","DOI":"10.1093\/brain\/awab171","type":"journal-article","created":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T11:36:32Z","timestamp":1631100992000},"page":"2798-2811","source":"Crossref","is-referenced-by-count":28,"title":["<i>SLITRK2<\/i>, an X-linked modifier of the age at onset in <i>C9orf72<\/i> frontotemporal lobar degeneration"],"prefix":"10.1093","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5154-2163","authenticated-orcid":false,"given":"Mathieu","family":"Barbier","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9, Institut du Cerveau-Paris Brain Institute-ICM, H\u00f4pital de la Salp\u00eatri\u00e8re, Inserm U 1127, CNRS UMR 7225, 75013, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"Camuzat","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Institut du Cerveau-Paris Brain Institute-ICM, H\u00f4pital de la Salp\u00eatri\u00e8re, Inserm U 1127, CNRS UMR 7225, 75013, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid","family":"El Hachimi","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Institut du Cerveau-Paris Brain Institute-ICM, H\u00f4pital de la Salp\u00eatri\u00e8re, Inserm U 1127, CNRS UMR 7225, 75013, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Guegan","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Institut du Cerveau-Paris Brain Institute-ICM, H\u00f4pital de la Salp\u00eatri\u00e8re, Inserm U 1127, CNRS UMR 7225, 75013, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisy","family":"Rinaldi","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Institut du Cerveau-Paris Brain Institute-ICM, H\u00f4pital de la Salp\u00eatri\u00e8re, Inserm U 1127, CNRS UMR 7225, 75013, Paris, France"},{"name":"Center for Rare or Early-Onset Dementias, IM2A, D\u00e9partement de Neurologie, AP-HP\u2014H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Lattante","sequence":"additional","affiliation":[{"name":"Sezione di Medicina Genomica, Dipartimento Scienze della Vita e Sanit\u00e0 Pubblica, Facolt\u00e0 di Medicina e Chirurgia, Universit\u00e0 Cattolica Sacro Cuore; U.O.C. Genetica Medica, Dipartimento di Scienze di Laboratorio e Infettivologico, Fondazione Policlinico Universitario \u2018A. Gemelli\u2019 IRCCS, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Houot","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Institut du Cerveau-Paris Brain Institute-ICM, H\u00f4pital de la Salp\u00eatri\u00e8re, Inserm U 1127, CNRS UMR 7225, 75013, Paris, France"},{"name":"Center for Rare or Early-Onset Dementias, IM2A, D\u00e9partement de Neurologie, AP-HP\u2014H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France"},{"name":"Centre of Excellence of Neurodegenerative Disease (CoEN), H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2216-1361","authenticated-orcid":false,"given":"Raquel","family":"S\u00e1nchez-Valle","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Cl\u00ednic, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Catalunya, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Sabatelli","sequence":"additional","affiliation":[{"name":"Adult NEMO Clinical Center, Unit of Neurology, Department of Aging, Neurological, Orthopedic and Head-Neck Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Section of Neurology, Department of Neuroscience, Faculty of Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Antonell","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Cl\u00ednic, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Catalunya, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Molina-Porcel","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Cl\u00ednic, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Catalunya, Spain"},{"name":"Neurological Tissue Bank of the Biobank-Hospital Clinic-IDIBAPS, Barcelona, Catalunya, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabienne","family":"Clot","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Fonctionnelle de Neurog\u00e9n\u00e9tique Mol\u00e9culaire et Cellulaire, D\u00e9partement de G\u00e9n\u00e9tique et Cytog\u00e9n\u00e9tique, AP-HP, H\u00f4pitaux Universitaires La Piti\u00e9 Salp\u00eatri\u00e8re-Charles Foix, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Couratier","sequence":"additional","affiliation":[{"name":"Centre D\u00e9mences rares University Hospital Limoges, Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"van der Ende","sequence":"additional","affiliation":[{"name":"Department of Neurology, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"van der Zee","sequence":"additional","affiliation":[{"name":"Neurodegenerative Brain Diseases Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium"},{"name":"Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Manzoni","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Camu","sequence":"additional","affiliation":[{"name":"Reference Centre for ALS, University Hospital Gui de Chauliac, University of Montpellier, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Cazeneuve","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Fonctionnelle de Neurog\u00e9n\u00e9tique Mol\u00e9culaire et Cellulaire, D\u00e9partement de G\u00e9n\u00e9tique et Cytog\u00e9n\u00e9tique, AP-HP, H\u00f4pitaux Universitaires La Piti\u00e9 Salp\u00eatri\u00e8re-Charles Foix, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Sellal","sequence":"additional","affiliation":[{"name":"Neurology Department, H\u00f4pitaux Civils de Colmar, France"},{"name":"INSERM U-1118, Strasbourg University, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Didic","sequence":"additional","affiliation":[{"name":"APHM, Timone, Service de Neurologie et Neuropsychologie, H\u00f4pital Timone Adultes, Marseille, France"},{"name":"Aix Marseille Univ, INSERM, INS, Inst Neurosci Syst, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Golfier","sequence":"additional","affiliation":[{"name":"Service de Neurologie, Centre Hospitalier Yves Le Foll, Saint Brieuc, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Pasquier","sequence":"additional","affiliation":[{"name":"University of Lille, Inserm UMRS1172, CHU, DISTAlz, LiCEND, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Duyckaerts","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Institut du Cerveau-Paris Brain Institute-ICM, H\u00f4pital de la Salp\u00eatri\u00e8re, Inserm U 1127, CNRS UMR 7225, 75013, Paris, France"},{"name":"Laboratoire de Neuropathologie Escourolle, H\u00f4pital de la Piti\u00e9-Salp\u00eatri\u00e8re, AP-HP, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomina","family":"Rossi","sequence":"additional","affiliation":[{"name":"Division of Neurology V and Neuropathology; Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalia C","family":"Bruni","sequence":"additional","affiliation":[{"name":"Regional Neurogenetic Centre, Department of Primary Care, ASP-CZ, Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00e9tica- Hospital Universitario Central de Asturias, Oviedo, Spain"},{"name":"Instituto de INvestigaci\u00f3n Biosanitaria del Principado de Asturias (ISPA), Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estrella","family":"G\u00f3mez-Tortosa","sequence":"additional","affiliation":[{"name":"Department of Neurology, Fundaci\u00f3n Jim\u00e9nez D\u00edaz, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"de Mendon\u00e7a","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Lisbon, Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Graff","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, Karolinska University Hospital-Huddinge, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6244-2096","authenticated-orcid":false,"given":"Mario","family":"Masellis","sequence":"additional","affiliation":[{"name":"Hurvitz Brain Sciences Program, Sunnybrook Research Institute; Department of Medicine (Neurology), Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedetta","family":"Nacmias","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy"},{"name":"IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Badreddine Mohand","family":"Oumoussa","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm, UMS Production et Analyse des donn\u00e9es en Sciences de la vie et en Sant\u00e9, PASS, Plateforme Post-g\u00e9nomique de la Piti\u00e9-Salp\u00eatri\u00e8re, P3S, F-75013, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludmila","family":"Jornea","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Institut du Cerveau-Paris Brain Institute-ICM, H\u00f4pital de la Salp\u00eatri\u00e8re, Inserm U 1127, CNRS UMR 7225, 75013, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Forlani","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Institut du Cerveau-Paris Brain Institute-ICM, H\u00f4pital de la Salp\u00eatri\u00e8re, Inserm U 1127, CNRS UMR 7225, 75013, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The French clinical and genetic Research network on FTLD\/FTLD-ALS and PREVDEMALS, The International Frontotemporal Dementia Genomics Consortium, The European Early Onset Dementia (EU -EOD) Consortium, Brainbank Neuro-CEB Neuropathology Network, Neurological Tissue Bank of the Biobank Hospital Clinic-IDIBAPS","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviana","family":"Van Deerlin","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D","family":"Rohrer","sequence":"additional","affiliation":[{"name":"Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Gelpi","sequence":"additional","affiliation":[{"name":"Neurological Tissue Bank of the Biobank-Hospital Clinic-IDIBAPS, Barcelona, Catalunya, Spain"},{"name":"Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Rademakers","sequence":"additional","affiliation":[{"name":"Neurodegenerative Brain Diseases Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Van Swieten","sequence":"additional","affiliation":[{"name":"Department of Neurology, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Le Guern","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Fonctionnelle de Neurog\u00e9n\u00e9tique Mol\u00e9culaire et Cellulaire, D\u00e9partement de G\u00e9n\u00e9tique et Cytog\u00e9n\u00e9tique, AP-HP, H\u00f4pitaux Universitaires La Piti\u00e9 Salp\u00eatri\u00e8re-Charles Foix, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Van Broeckhoven","sequence":"additional","affiliation":[{"name":"Neurodegenerative Brain Diseases Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium"},{"name":"Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Ferrari","sequence":"additional","affiliation":[{"name":"University College London, Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"G\u00e9nin","sequence":"additional","affiliation":[{"name":"G\u00e9n\u00e9tique, G\u00e9nomique Fonctionnelle et Biotechnologies, Facult\u00e9 de M\u00e9decine, Univ Brest, Inserm UMR1078, Brest, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Brice","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Institut du Cerveau-Paris Brain Institute-ICM, H\u00f4pital de la Salp\u00eatri\u00e8re, Inserm U 1127, CNRS UMR 7225, 75013, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Le Ber","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Institut du Cerveau-Paris Brain Institute-ICM, H\u00f4pital de la Salp\u00eatri\u00e8re, Inserm U 1127, CNRS UMR 7225, 75013, Paris, France"},{"name":"Center for Rare or Early-Onset Dementias, IM2A, D\u00e9partement de Neurologie, AP-HP\u2014H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,10,21]]},"reference":[{"issue":"6686","key":"2021103110135932900_awab171-B1","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/31508","article-title":"Association of missense and 5\u2019-splice-site mutations in tau with the inherited dementia FTDP-17","volume":"393","author":"Hutton","year":"1998","journal-title":"Nature"},{"issue":"7105","key":"2021103110135932900_awab171-B2","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1038\/nature05016","article-title":"Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17","volume":"442","author":"Baker","year":"2006","journal-title":"Nature"},{"issue":"7105","key":"2021103110135932900_awab171-B3","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1038\/nature05017","article-title":"Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21","volume":"442","author":"Cruts","year":"2006","journal-title":"Nature"},{"issue":"2","key":"2021103110135932900_awab171-B4","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.neuron.2011.09.011","article-title":"Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS","volume":"72","author":"DeJesus-Hernandez","year":"2011","journal-title":"Neuron"},{"issue":"2","key":"2021103110135932900_awab171-B5","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.neuron.2011.09.010","article-title":"A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD","volume":"72","author":"Renton","year":"2011","journal-title":"Neuron"},{"issue":"47","key":"2021103110135932900_awab171-B6","doi-asserted-by":"crossref","first-page":"E4530","DOI":"10.1073\/pnas.1318835110","article-title":"Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration","volume":"110","author":"Lagier-Tourenne","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"2021103110135932900_awab171-B7","doi-asserted-by":"crossref","first-page":"e203","DOI":"10.1212\/NXG.0000000000000203","article-title":"Factors influencing the age at onset in familial frontotemporal lobar dementia: Important weight of genetics","volume":"3","author":"Barbier","year":"2017","journal-title":"Neurol Genet"},{"issue":"3","key":"2021103110135932900_awab171-B8","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s00401-015-1445-9","article-title":"Semi-automated quantification of C9orf72 expansion size reveals inverse correlation between hexanucleotide repeat number and disease duration in frontotemporal degeneration","volume":"130","author":"Suh","year":"2015","journal-title":"Acta Neuropathol"},{"key":"2021103110135932900_awab171-B9","doi-asserted-by":"crossref","first-page":"234.e1","DOI":"10.1016\/j.neurobiolaging.2018.09.010","article-title":"Relations between C9orf72 expansion size in blood, age at onset, age at collection and transmission across generations in patients and presymptomatic carriers","volume":"74","author":"Fournier","year":"2019","journal-title":"Neurobiol Aging"},{"issue":"1","key":"2021103110135932900_awab171-B10","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13024-020-0359-8","article-title":"Elevated methylation levels, reduced expression levels, and frequent contractions in a clinical cohort of C9orf72 expansion carriers","volume":"15","author":"Jackson","year":"2020","journal-title":"Mol Neurodegener"},{"issue":"3","key":"2021103110135932900_awab171-B11","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/ng.536","article-title":"Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions","volume":"42","author":"Van Deerlin","year":"2010","journal-title":"Nat Genet"},{"issue":"3","key":"2021103110135932900_awab171-B12","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s00401-013-1239-x","article-title":"TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexanucleotide repeat expansions","volume":"127","author":"Gallagher","year":"2014","journal-title":"Acta Neuropathol"},{"issue":"3","key":"2021103110135932900_awab171-B13","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s00401-013-1240-4","article-title":"TMEM106B protects C9ORF72 expansion carriers against frontotemporal dementia","volume":"127","author":"van Blitterswijk","year":"2014","journal-title":"Acta Neuropathol"},{"issue":"11","key":"2021103110135932900_awab171-B14","doi-asserted-by":"crossref","first-page":"2658.e1-5","DOI":"10.1016\/j.neurobiolaging.2014.06.023","article-title":"Defining the association of TMEM106B variants among frontotemporal lobar degeneration patients with GRN mutations and C9orf72 repeat expansions","volume":"35","author":"Lattante","year":"2014","journal-title":"Neurobiol Aging"},{"issue":"10","key":"2021103110135932900_awab171-B15","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.1093\/brain\/awy238","article-title":"A C6orf10\/LOC101929163 locus is associated with age of onset in C9orf72 carriers","volume":"141","author":"Zhang","year":"2018","journal-title":"Brain"},{"key":"2021103110135932900_awab171-B16","doi-asserted-by":"crossref","DOI":"10.1016\/j.neurobiolaging.2020.07.021","article-title":"No association of CpG SNP rs9357140 with onset age in Belgian C9orf72 repeat expansion carriers","volume":"97","author":"Ko\u00e7o\u011flu","year":"2021","journal-title":"Neurobiol Aging"},{"issue":"11","key":"2021103110135932900_awab171-B17","doi-asserted-by":"crossref","first-page":"3051","DOI":"10.1093\/brain\/awl288","article-title":"Demographic, neurological and behavioural characteristics and brain perfusion SPECT in frontal variant of frontotemporal dementia","volume":"129","author":"Le Ber","year":"2006","journal-title":"Brain"},{"issue":"12","key":"2021103110135932900_awab171-B18","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1038\/s41431-018-0164-9","article-title":"Association of modifiers and other genetic factors explain Marfan syndrome clinical variability","volume":"26","author":"Aubart","year":"2018","journal-title":"Eur J Hum Genet"},{"issue":"7","key":"2021103110135932900_awab171-B19","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/S1474-4422(14)70065-1","article-title":"Frontotemporal dementia and its subtypes: A genome-wide association study","volume":"13","author":"Ferrari","year":"2014","journal-title":"Lancet Neurol"},{"key":"2021103110135932900_awab171-B20","doi-asserted-by":"crossref","first-page":"167.e1-167.e9","DOI":"10.1016\/j.neurobiolaging.2020.02.014","article-title":"Plasma progranulin levels for frontotemporal dementia in clinical practice: A 10-year French experience","volume":"91","author":"Sellami","year":"2020","journal-title":"Neurobiol Aging"},{"issue":"1","key":"2021103110135932900_awab171-B21","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/ng786","article-title":"Merlin\u2013rapid analysis of dense genetic maps using sparse gene flow trees","volume":"30","author":"Abecasis","year":"2002","journal-title":"Nat Genet"},{"issue":"7","key":"2021103110135932900_awab171-B22","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1038\/ng.2310","article-title":"Genome-wide efficient mixed-model analysis for association studies","volume":"44","author":"Zhou","year":"2012","journal-title":"Nat Genet"},{"issue":"10","key":"2021103110135932900_awab171-B23","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1093\/bioinformatics\/btm108","article-title":"GenABEL: An R library for genome-wide association analysis","volume":"23","author":"Aulchenko","year":"2007","journal-title":"Bioinformatics"},{"issue":"3","key":"2021103110135932900_awab171-B24","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: A tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am J Hum Genet"},{"key":"2021103110135932900_awab171-B25","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13742-015-0047-8","article-title":"Second-generation PLINK: Rising to the challenge of larger and richer datasets","volume":"4","author":"Chang","year":"2015","journal-title":"Gigascience"},{"issue":"4","key":"2021103110135932900_awab171-B26","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1111\/j.0006-341X.2000.01016.x","article-title":"Estimation of multivariate frailty models using penalized partial likelihood","volume":"56","author":"Ripatti","year":"2000","journal-title":"Biometrics"},{"key":"2021103110135932900_awab171-B27","doi-asserted-by":"crossref","first-page":"9686","DOI":"10.1038\/srep09686","article-title":"Structure of Slitrk2-PTP\u03b4 complex reveals mechanisms for splicing-dependent trans-synaptic adhesion","volume":"5","author":"Yamagata","year":"2015","journal-title":"Sci Rep"},{"issue":"5","key":"2021103110135932900_awab171-B28","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.ajhg.2013.03.017","article-title":"eXclusion: Toward integrating the X chromosome in genome-wide association analyses","volume":"92","author":"Wise","year":"2013","journal-title":"Am J Hum Genet"},{"issue":"6","key":"2021103110135932900_awab171-B29","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1002\/gepi.22132","article-title":"Statistics for X-chromosome associations","volume":"42","author":"\u00d6zbek","year":"2018","journal-title":"Genet Epidemiol"},{"issue":"2","key":"2021103110135932900_awab171-B30","doi-asserted-by":"crossref","first-page":"485","DOI":"10.3233\/JAD-121456","article-title":"C9ORF72 repeat expansions in the frontotemporal dementias spectrum of diseases: A flow-chart for genetic testing","volume":"34","author":"Le Ber","year":"2013","journal-title":"J Alzheimers Dis"},{"issue":"1","key":"2021103110135932900_awab171-B31","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1038\/s41598-017-02364-1","article-title":"Age-related penetrance of the C9orf72 repeat expansion","volume":"7","author":"Murphy","year":"2017","journal-title":"Sci Rep"},{"key":"2021103110135932900_awab171-B32","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.sbi.2019.01.010","article-title":"Synaptic organizer: Slitrks and type IIa receptor protein tyrosine phosphatases","volume":"54","author":"Won","year":"2019","journal-title":"Curr Opin Struct Biol"},{"issue":"1","key":"2021103110135932900_awab171-B33","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S1044-7431(03)00129-5","article-title":"Identification and characterization of Slitrk, a novel neuronal transmembrane protein family controlling neurite outgrowth","volume":"24","author":"Aruga","year":"2003","journal-title":"Mol Cell Neurosci"},{"issue":"1","key":"2021103110135932900_awab171-B34","doi-asserted-by":"crossref","first-page":"17094","DOI":"10.1038\/s41598-019-53519-1","article-title":"Slitrk2 controls excitatory synapse development via PDZ-mediated protein interactions","volume":"9","author":"Han","year":"2019","journal-title":"Sci Rep"},{"issue":"7","key":"2021103110135932900_awab171-B35","doi-asserted-by":"crossref","first-page":"2374","DOI":"10.1016\/j.celrep.2020.01.084","article-title":"Opposite control of excitatory and inhibitory synapse formation by slitrk2 and slitrk5 on dopamine neurons modulates hyperactivity behavior","volume":"30","author":"Salesse","year":"2020","journal-title":"Cell Rep"},{"issue":"208","key":"2021103110135932900_awab171-B36","doi-asserted-by":"crossref","first-page":"208ra149","DOI":"10.1126\/scitranslmed.3007529","article-title":"Targeting RNA foci in iPSC-derived motor neurons from ALS patients with a C9ORF72 repeat expansion","volume":"5","author":"Sareen","year":"2013","journal-title":"Sci Transl Med"},{"key":"2021103110135932900_awab171-B37","doi-asserted-by":"crossref","first-page":"69","DOI":"10.4137\/JCNSD.S18103","article-title":"Molecular network analysis suggests a logical hypothesis for the pathological role of c9orf72 in amyotrophic lateral sclerosis\/frontotemporal dementia","volume":"6","author":"Satoh","year":"2014","journal-title":"J Cent Nerv Syst Dis"},{"issue":"1","key":"2021103110135932900_awab171-B38","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/s40478-019-0797-0","article-title":"Extensive transcriptomic study emphasizes importance of vesicular transport in C9orf72 expansion carriers","volume":"7","author":"Dickson","year":"2019","journal-title":"Acta Neuropathol Commun"},{"issue":"1","key":"2021103110135932900_awab171-B39","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1186\/s40478-019-0812-5","article-title":"Synaptic localization of C9orf72 regulates post-synaptic glutamate receptor 1 levels","volume":"7","author":"Xiao","year":"2019","journal-title":"Acta Neuropathol Commun"},{"issue":"1","key":"2021103110135932900_awab171-B40","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s40478-018-0579-0","article-title":"Novel antibodies reveal presynaptic localization of C9orf72 protein and reduced protein levels in C9orf72 mutation carriers","volume":"6","author":"Frick","year":"2018","journal-title":"Acta Neuropathol Commun"},{"issue":"1","key":"2021103110135932900_awab171-B41","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/s41467-017-02729-0","article-title":"C9ORF72 repeat expansion causes vulnerability of motor neurons to Ca2+-permeable AMPA receptor-mediated excitotoxicity","volume":"9","author":"Selvaraj","year":"2018","journal-title":"Nat Commun"},{"issue":"5","key":"2021103110135932900_awab171-B42","doi-asserted-by":"crossref","first-page":"e10722","DOI":"10.15252\/emmm.201910722","article-title":"Synaptic dysfunction induced by glycine-alanine dipeptides in C9orf72-ALS\/FTD is rescued by SV2 replenishment","volume":"12","author":"Jensen","year":"2020","journal-title":"EMBO Mol Med"}],"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/brain\/article-pdf\/144\/9\/2798\/40880432\/awab171.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/brain\/article-pdf\/144\/9\/2798\/40880432\/awab171.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,31]],"date-time":"2021-10-31T10:16:22Z","timestamp":1635675382000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/article\/144\/9\/2798\/6408768"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,1]]},"references-count":42,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,10,21]]},"published-print":{"date-parts":[[2021,10,22]]}},"URL":"https:\/\/doi.org\/10.1093\/brain\/awab171","relation":{},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,9,1]]},"published":{"date-parts":[[2021,9,1]]}}}