Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia.
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Gialluisi A
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
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Andlauer TFM
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
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Mirza-Schreiber N
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
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Moll K
Department of Child and Adolescent Psychiatry, Psychosomatic, and Psychotherapy, Ludwig-Maximilians University, Munich, Germany.
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Becker J
Institute of Human Genetics, University of Bonn, Bonn, Germany.
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Hoffmann P
Institute of Human Genetics, University of Bonn, Bonn, Germany.
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Ludwig KU
Institute of Human Genetics, University of Bonn, Bonn, Germany.
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Czamara D
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
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St Pourcain B
Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, Netherlands.
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Brandler W
University of California San Diego, Department of Psychiatry, San Diego, CA, USA.
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Honbolygó F
Brain Imaging Centre, Research Centre of Natural Sciences of the Hungarian Academy of Sciences, Budapest, Hungary.
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Tóth D
Brain Imaging Centre, Research Centre of Natural Sciences of the Hungarian Academy of Sciences, Budapest, Hungary.
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Csépe V
Brain Imaging Centre, Research Centre of Natural Sciences of the Hungarian Academy of Sciences, Budapest, Hungary.
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Huguet G
Human Genetics and Cognitive Functions Unit, Institut Pasteur, Paris, France.
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Morris AP
Department of Biostatistics, Universiy of Liverpool, Liverpool, UK.
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Hulslander J
Institute for Behavioral Genetics and Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
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Willcutt EG
Institute for Behavioral Genetics and Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
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DeFries JC
Institute for Behavioral Genetics and Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
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Olson RK
Institute for Behavioral Genetics and Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
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Smith SD
Developmental Neuroscience Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE, USA.
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Pennington BF
Developmental Neuropsychology Lab & Clinic, Department of Psychology, University of Denver, Denver, CO, USA.
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Vaessen A
Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience & Maastricht Brain Imaging Center (M-BIC), Maastricht University, Maastricht, Netherlands.
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Maurer U
Department of Psychology, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
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Lyytinen H
Centre for Research on Learning and Teaching, Department of Psychology, University of Jyväskylä, Jyväskylä, Finland.
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Peyrard-Janvid M
Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
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Leppänen PHT
Centre for Research on Learning and Teaching, Department of Psychology, University of Jyväskylä, Jyväskylä, Finland.
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Brandeis D
Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, Zurich, Switzerland.
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Bonte M
Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience & Maastricht Brain Imaging Center (M-BIC), Maastricht University, Maastricht, Netherlands.
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Stein JF
Department of Physiology, University of Oxford, Oxford, UK.
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Talcott JB
School of Life and Health Sciences, Aston University, Birmingham, UK.
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Fauchereau F
Human Genetics and Cognitive Functions Unit, Institut Pasteur, Paris, France.
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Wilcke A
Cognitive Genetics Unit, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.
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Francks C
Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, Netherlands.
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Bourgeron T
Human Genetics and Cognitive Functions Unit, Institut Pasteur, Paris, France.
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Monaco AP
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
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Ramus F
Laboratoire de Sciences Cognitives et Psycholinguistique, Ecole Normale Supérieure, CNRS, EHESS, PSL Research University, Paris, France.
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Landerl K
Institute of Psychology, University of Graz, Graz, Austria and BioTechMed, Graz, Austria.
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Kere J
Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
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Scerri TS
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
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Paracchini S
School of Medicine, University of St Andrews, St Andrews, UK.
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Fisher SE
Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, Netherlands.
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Schumacher J
Institute of Human Genetics, University of Bonn, Bonn, Germany.
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Nöthen MM
Institute of Human Genetics, University of Bonn, Bonn, Germany.
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Müller-Myhsok B
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany. bmm@psych.mpg.de.
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Schulte-Körne G
Department of Child and Adolescent Psychiatry, Psychosomatic, and Psychotherapy, Ludwig-Maximilians University, Munich, Germany. Gerd.Schulte-Koerne@med.uni-muenchen.de.
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Published in:
- Translational psychiatry. - 2019
English
Developmental dyslexia (DD) is one of the most prevalent learning disorders, with high impact on school and psychosocial development and high comorbidity with conditions like attention-deficit hyperactivity disorder (ADHD), depression, and anxiety. DD is characterized by deficits in different cognitive skills, including word reading, spelling, rapid naming, and phonology. To investigate the genetic basis of DD, we conducted a genome-wide association study (GWAS) of these skills within one of the largest studies available, including nine cohorts of reading-impaired and typically developing children of European ancestry (N = 2562-3468). We observed a genome-wide significant effect (p < 1 × 10-8) on rapid automatized naming of letters (RANlet) for variants on 18q12.2, within MIR924HG (micro-RNA 924 host gene; rs17663182 p = 4.73 × 10-9), and a suggestive association on 8q12.3 within NKAIN3 (encoding a cation transporter; rs16928927, p = 2.25 × 10-8). rs17663182 (18q12.2) also showed genome-wide significant multivariate associations with RAN measures (p = 1.15 × 10-8) and with all the cognitive traits tested (p = 3.07 × 10-8), suggesting (relational) pleiotropic effects of this variant. A polygenic risk score (PRS) analysis revealed significant genetic overlaps of some of the DD-related traits with educational attainment (EDUyears) and ADHD. Reading and spelling abilities were positively associated with EDUyears (p ~ [10-5-10-7]) and negatively associated with ADHD PRS (p ~ [10-8-10-17]). This corroborates a long-standing hypothesis on the partly shared genetic etiology of DD and ADHD, at the genome-wide level. Our findings suggest new candidate DD susceptibility genes and provide new insights into the genetics of dyslexia and its comorbities.
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Open access status
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gold
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https://folia.unifr.ch/global/documents/88688
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