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Eur J Hum Genet. 2014 May;22(5):675-80. doi: 10.1038/ejhg.2013.199. Epub 2013 Sep 11.

Genetic analysis of dyslexia candidate genes in the European cross-linguistic NeuroDys cohort.

Author information

1
1] Institute of Human Genetics, University of Bonn, Bonn, Germany [2] Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
2
1] Max Planck Institute of Psychiatry, Munich, Germany [2] Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
3
1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK [2] Walter and Eliza Hall Institute for Medical Research, Melbourne, Victoria, Australia.
4
Laboratoire de Sciences Cognitives et Psycholinguistique, Ecole Normale Supérieure, CNRS, EHESS, Paris, France.
5
Institute of Cognitive Neuroscience and Psychology, Research Centre of Natural Sciences of the Hungarian Academy of Sciences Budapest, Budapest, Hungary.
6
School of Life and Health Sciences, Aston University, Birmingham, UK.
7
Department of Physiology, University of Oxford, Oxford, UK.
8
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
9
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.
10
1] Human Genetics and Cognitive Functions, CNRS URA 2182, Institut Pasteur, Paris, France [2] Sorbonne Paris Cité, Université Paris Diderot, Paris, France.
11
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.
12
1] Unité de Neurologie Pédiatrique, Hôpital des Enfants, Toulouse, France [2] Inserm U825, Hôpital Purpan, Toulouse, France.
13
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.
14
Centre de Référence sur les Troubles des Apprentissages, Hôpital Bicêtre, Paris, France.
15
Centre de Référence des Troubles d'apprentissage, CHU Timone, Marseille, France.
16
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.
17
Service de Psychopathologie de l'enfant et de l'adolescent, Hôpital Robert Debré, APHP, Paris, France.
18
Department of Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland.
19
1] TUM-Neuroimaging Center, Technische Universität München, Munich, Germany [2] Department of Neurology, Technische Universität München, Munich, Germany.
20
Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience & Maastricht Brain Imaging Institute (M-BIC), Maastricht University, Maastricht, The Netherlands.
21
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.
22
Finnish Center of Excellence in Learning and Motivation Research, Department of Psychology, University of Jyväskylä, Jyväskylä, Finland.
23
Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
24
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.
25
Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Ludwig-Maximilians-University Munich, Munich, Germany.
26
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.
27
Department of Psychology, University of Graz, Graz, Austria.
28
1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK [2] School of Medicine, University of St Andrews, St Andrews, UK.
29
Institute of Human Genetics, University of Bonn, Bonn, Germany.

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.

PMID:
24022301
PMCID:
PMC3992562
DOI:
10.1038/ejhg.2013.199
[Indexed for MEDLINE]
Free PMC Article
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