title: Genetic analysis of dyslexia candidate genes in the European cross-linguistic NeuroDys cohort.
abstract: Dyslexia is one of the most common childhood disorders with a prevalence of around 5-10% in school-age children. Although an important genetic component is known to have a role in the aetiology of dyslexia, we are far from understanding the molecular mechanisms leading to the disorder. Several candidate genes have been implicated in dyslexia, including DYX1C1, DCDC2, KIAA0319, and the MRPL19/C2ORF3 locus, each with reports of both positive and no replications. We generated a European cross-linguistic sample of school-age children - the NeuroDys cohort - that includes more than 900 individuals with dyslexia, sampled with homogenous inclusion criteria across eight European countries, and a comparable number of controls. Here, we describe association analysis of the dyslexia candidate genes/locus in the NeuroDys cohort. We performed both case-control and quantitative association analyses of single markers and haplotypes previously reported to be dyslexia-associated. Although we observed association signals in samples from single countries, we did not find any marker or haplotype that was significantly associated with either case-control status or quantitative measurements of word-reading or spelling in the meta-analysis of all eight countries combined. Like in other neurocognitive disorders, our findings underline the need for larger sample sizes to validate possibly weak genetic effects.
authors.affiliation: 1] Institute of Human Genetics, University of Bonn, Bonn, Germany [2] Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Becker
authors.affiliation: 1] Max Planck Institute of Psychiatry, Munich, Germany [2] Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
authors.forename: Darina
authors.initials: D
authors.lastname: Czamara
authors.affiliation: 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK [2] Walter and Eliza Hall Institute for Medical Research, Melbourne, Victoria, Australia.
authors.forename: Tom S
authors.initials: TS
authors.lastname: Scerri
authors.affiliation: Laboratoire de Sciences Cognitives et Psycholinguistique, Ecole Normale Supérieure, CNRS, EHESS, Paris, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Ramus
authors.affiliation: Institute of Cognitive Neuroscience and Psychology, Research Centre of Natural Sciences of the Hungarian Academy of Sciences Budapest, Budapest, Hungary.
authors.forename: Valéria
authors.initials: V
authors.lastname: Csépe
authors.affiliation: School of Life and Health Sciences, Aston University, Birmingham, UK.
authors.forename: Joel B
authors.initials: JB
authors.lastname: Talcott
authors.affiliation: Department of Physiology, University of Oxford, Oxford, UK.
authors.forename: John
authors.initials: J
authors.lastname: Stein
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Morris
authors.affiliation: 1] Institute of Human Genetics, University of Bonn, Bonn, Germany [2] Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Kerstin U
authors.initials: KU
authors.lastname: Ludwig
authors.affiliation: 1] Institute of Human Genetics, University of Bonn, Bonn, Germany [2] Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany [3] Division of Medical Genetics, University Hospital and Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Per
authors.identifier: 000000026573983X
authors.initials: P
authors.lastname: Hoffmann
authors.affiliation: Institute of Cognitive Neuroscience and Psychology, Research Centre of Natural Sciences of the Hungarian Academy of Sciences Budapest, Budapest, Hungary.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Honbolygó
authors.affiliation: Institute of Cognitive Neuroscience and Psychology, Research Centre of Natural Sciences of the Hungarian Academy of Sciences Budapest, Budapest, Hungary.
authors.forename: Dénes
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authors.lastname: Tóth
authors.affiliation: 1] Human Genetics and Cognitive Functions, CNRS URA 2182, Institut Pasteur, Paris, France [2] Sorbonne Paris Cité, Université Paris Diderot, Paris, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Fauchereau
authors.affiliation: Laboratoire de Sciences Cognitives et Psycholinguistique, Ecole Normale Supérieure, CNRS, EHESS, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bogliotti
authors.affiliation: 1] Unité de Neurologie Pédiatrique, Hôpital des Enfants, Toulouse, France [2] Inserm U825, Hôpital Purpan, Toulouse, France [3] Centre de Référence sur les Troubles des Apprentissages, Hôpital Bicêtre, Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Iannuzzi
authors.affiliation: 1] Unité de Neurologie Pédiatrique, Hôpital des Enfants, Toulouse, France [2] Inserm U825, Hôpital Purpan, Toulouse, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Chaix
authors.affiliation: 1] Laboratoire de Psychologie et NeuroCognition UMR 5105 CNRS, Université Pierre Mendès France, Grenoble, France [2] Centre référent pour le diagnostic des troubles du langage et des apprentissages, Département de pédiatrie, CHU Nord, Grenoble, France.
authors.forename: Sylviane
authors.initials: S
authors.lastname: Valdois
authors.affiliation: Centre de Référence sur les Troubles des Apprentissages, Hôpital Bicêtre, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Billard
authors.affiliation: Centre de Référence des Troubles d'apprentissage, CHU Timone, Marseille, France.
authors.forename: Florence
authors.initials: F
authors.lastname: George
authors.affiliation: 1] Centre de Référence pour les Troubles des Apprentissages, Hospices Civils de Lyon, Hôpital E Herriot, Lyon, France [2] Centre Hospitalier Le Vinatier, Bron, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Soares-Boucaud
authors.affiliation: Service de Psychopathologie de l'enfant et de l'adolescent, Hôpital Robert Debré, APHP, Paris, France.
authors.forename: Christophe-Loïc
authors.initials: CL
authors.lastname: Gérard
authors.affiliation: Department of Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland.
authors.forename: Sanne
authors.initials: S
authors.lastname: van der Mark
authors.affiliation: 1] TUM-Neuroimaging Center, Technische Universität München, Munich, Germany [2] Department of Neurology, Technische Universität München, Munich, Germany.
authors.forename: Enrico
authors.initials: E
authors.lastname: Schulz
authors.affiliation: Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience & Maastricht Brain Imaging Institute (M-BIC), Maastricht University, Maastricht, The Netherlands.
authors.forename: Anniek
authors.initials: A
authors.lastname: Vaessen
authors.affiliation: 1] Department of Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland [2] Department of Psychology, University of Zurich, Zurich, Switzerland [3] Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland.
authors.forename: Urs
authors.initials: U
authors.lastname: Maurer
authors.affiliation: Finnish Center of Excellence in Learning and Motivation Research, Department of Psychology, University of Jyväskylä, Jyväskylä, Finland.
authors.forename: Kaisa
authors.initials: K
authors.lastname: Lohvansuu
authors.affiliation: Finnish Center of Excellence in Learning and Motivation Research, Department of Psychology, University of Jyväskylä, Jyväskylä, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Lyytinen
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Marco
authors.initials: M
authors.lastname: Zucchelli
authors.affiliation: 1] Department of Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland [2] Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland [3] Zurich Center for Integrative Human Physiology (ZIHP), Zurich, Switzerland [4] Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Brandeis
authors.affiliation: Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience & Maastricht Brain Imaging Institute (M-BIC), Maastricht University, Maastricht, The Netherlands.
authors.forename: Leo
authors.initials: L
authors.lastname: Blomert
authors.affiliation: Finnish Center of Excellence in Learning and Motivation Research, Department of Psychology, University of Jyväskylä, Jyväskylä, Finland.
authors.forename: Paavo H T
authors.initials: PH
authors.lastname: Leppänen
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bruder
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Monaco
authors.affiliation: 1] Max Planck Institute of Psychiatry, Munich, Germany [2] Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
authors.forename: Bertram
authors.initials: B
authors.lastname: Müller-Myhsok
authors.affiliation: 1] Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden [2] Molecular Medicine Program, Biomedicum, University of Helsinki and Folkhälsan Institute of Genetics, Helsinki, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
authors.affiliation: Department of Psychology, University of Graz, Graz, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Landerl
authors.affiliation: 1] Institute of Human Genetics, University of Bonn, Bonn, Germany [2] Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Schulte-Körne
authors.affiliation: 1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK [2] School of Medicine, University of St Andrews, St Andrews, UK.
authors.forename: Silvia
authors.initials: S
authors.lastname: Paracchini
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Myriam
authors.initials: M
authors.lastname: Peyrard-Janvid
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Johannes
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authors.lastname: Schumacher
mesh_terms: D016022:Case-Control Studies; D004410:Dyslexia / Q000235:genetics*; D056726:Genetic Association Studies; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015201:Meta-Analysis as Topic; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable
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