Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental 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
Department of Genomics, Life and Brain Center, Institute of Human Genetics, University of Bonn, Bonn, Germany.
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Hoffmann P
Department of Genomics, Life and Brain Center, Institute of Human Genetics, University of Bonn, Bonn, Germany.
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Ludwig KU
Department of Genomics, Life and Brain Center, 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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Pourcain BS
Language and Genetics Department, Max Planck Institute for Psycholinguistics and Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
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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 and University Paris Diderot, Sorbonne Paris Cité, Paris, France.
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Chaix Y
ToNIC, Toulouse NeuroImaging Center, Université de Toulouse, Inserm, UPS, Toulouse, France.
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Iannuzzi S
Children's Hospital, Purpan University Hospital, Toulouse, France.
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Demonet JF
Leenaards Memory Centre, Department of Clinical Neurosciences Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.
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Morris AP
Department of Biostatistics, University 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
Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
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Pennington BF
Developmental Neuropsychology Lab and 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 and Maastricht Brain Imaging Center (M-BIC), Maastricht University, Maastricht, The 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 and Maastricht Brain Imaging Center (M-BIC), Maastricht University, Maastricht, The 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 and University Paris Diderot, Sorbonne Paris Cité, Paris, France.
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Wilcke A
Cognitive Genetics Unit, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.
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Kirsten H
Cognitive Genetics Unit, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.
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Müller B
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 and Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
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Bourgeron T
Human Genetics and Cognitive Functions Unit, Institut Pasteur and University Paris Diderot, Sorbonne Paris Cité, Paris, France.
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Monaco AP
Wellcome 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 University, Paris, France.
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Landerl K
Institute of Psychology, University of Graz 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 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 and Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
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Schumacher J
Department of Genomics, Life and Brain Center, Institute of Human Genetics, University of Bonn, Bonn, Germany.
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Nöthen MM
Department of Genomics, Life and Brain Center, 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:
- Molecular psychiatry. - 2020
English
Developmental dyslexia (DD) is a learning disorder affecting the ability to read, with a heritability of 40-60%. A notable part of this heritability remains unexplained, and large genetic studies are warranted to identify new susceptibility genes and clarify the genetic bases of dyslexia. We carried out a genome-wide association study (GWAS) on 2274 dyslexia cases and 6272 controls, testing associations at the single variant, gene, and pathway level, and estimating heritability using single-nucleotide polymorphism (SNP) data. We also calculated polygenic scores (PGSs) based on large-scale GWAS data for different neuropsychiatric disorders and cortical brain measures, educational attainment, and fluid intelligence, testing them for association with dyslexia status in our sample. We observed statistically significant (p < 2.8 × 10-6) enrichment of associations at the gene level, for LOC388780 (20p13; uncharacterized gene), and for VEPH1 (3q25), a gene implicated in brain development. We estimated an SNP-based heritability of 20-25% for DD, and observed significant associations of dyslexia risk with PGSs for attention deficit hyperactivity disorder (at pT = 0.05 in the training GWAS: OR = 1.23[1.16; 1.30] per standard deviation increase; p = 8 × 10-13), bipolar disorder (1.53[1.44; 1.63]; p = 1 × 10-43), schizophrenia (1.36[1.28; 1.45]; p = 4 × 10-22), psychiatric cross-disorder susceptibility (1.23[1.16; 1.30]; p = 3 × 10-12), cortical thickness of the transverse temporal gyrus (0.90[0.86; 0.96]; p = 5 × 10-4), educational attainment (0.86[0.82; 0.91]; p = 2 × 10-7), and intelligence (0.72[0.68; 0.76]; p = 9 × 10-29). This study suggests an important contribution of common genetic variants to dyslexia risk, and novel genomic overlaps with psychiatric conditions like bipolar disorder, schizophrenia, and cross-disorder susceptibility. Moreover, it revealed the presence of shared genetic foundations with a neural correlate previously implicated in dyslexia by neuroimaging evidence.
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hybrid
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https://folia.unifr.ch/global/documents/169357
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