Title

Genome-wide Association Scan Identifies New Variants Associated with a Cognitive Predictor of Dyslexia

Authors

Alessandro Gialluisi, Max Planck Institute of Psychiatry, Munich
Till F. M. Andlauer, Max Planck Institute of Psychiatry, Munich
Nazanin Mirza-Schreiber, Max Planck Institute of Psychiatry, Munich
Kristina Moll, Ludwig-Maximilians University, Munich
Jessica Becker, University of Bonn
Per Hoffmann, University of Bonn
Kerstin U. Ludwig, University of Bonn
Darina Czamara, Max Planck Institute of Psychiatry, Munich
Beate St Pourcain, Max Planck Institute for Psycholinguistics, Radboud University, University of Bristol
William Brandler, University of California San Diego
Ferenc Honbolygó, Research Centre of Natural Sciences of the Hungarian Academy of Sciences
Dénes Tóth, Research Centre of Natural Sciences of the Hungarian Academy of Sciences
Valéria Csépe, Research Centre of Natural Sciences of the Hungarian Academy of Sciences
Guillaume Huguet, Institut Pasteur, Sorbonne Paris Cité
Andrew P. Morris, Universiy of Liverpool, University of Oxford
Jacqueline Hulslander, University of Colorado Boulder
Erik G. Willcutt, University of Colorado Boulder
John C. DeFries, University of Colorado Boulder
Richard K. Olson, University of Colorado Boulder
Shelley D. Smith, University of Nebraska Medical Center
Bruce F. Pennington, University of DenverFollow
Anniek Vaessen, Maastricht University
Urs Maurer, The Chinese University of Hong Kong,
Heikki Lyytinen, University of Jyväskylä
Myriam Peyrard-Janvid, Karolinska Institutet
Paavo H. T. Leppänen, University of Jyväskylä
Daniel Brandeis, University of Zurich, Mannheim/Heidelberg University,
Milene Bonte, Maastricht University
John F. Stein, University of Oxford
Joel B. Talcott, Aston University
Fabien Fauchereau, Institut Pasteur, Sorbonne Paris Cité
Arndt Wilcke, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig
Clyde Francks, Max Planck Institute for Psycholinguistics, Radboud University
Thomas Bourgeron, Institut Pasteur, Sorbonne Paris Cité
Anthony P. Monaco, University of Oxford, Tufts University
Franck Ramus, PSL Research University
Karin Landerl, University of Graz, BioTechMed
Juha Kere, Karolinska Institutet, University of Helsinki, King’s College London
Thomas S. Scerri, University of Oxford, The Walter and Eliza Hall Institute of Medical Research & Melbourne University
Silvia Paracchini, University of St Andrews
Simon E. Fisher, Max Planck Institute for Psycholinguistics, Radboud University
Johannes Schumacher, University of Bonn
Markus M. Nöthen, University of Bonn
Bertram Müller-Myhsok, Max Planck Institute of Psychiatry, Munich, University of Liverpool
Gerd Schulte-Körne, Ludwig-Maximilians University

Document Type

Article

Publication Date

2-11-2019

Organizational Units

College of Arts Humanities and Social Sciences, Psychology

Abstract

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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