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

Publication Date

2-11-2019

Document Type

Article

Organizational Units

College of Arts Humanities and Social Sciences, Psychology

Keywords

Developmental dyslexia (DD), Genome-wide association study (GWAS), Cognitive skills

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.

Copyright Date

2-11-2019

Copyright Statement / License for Reuse

This work is licensed under a Creative Commons Attribution 4.0 International License.

Rights Holder

Alessandro Gialluisi, Till F. M. Andlauer, Nazanin Mira-Schreiber, Kristina Moll, Jessica Becker, Per Hoffman, Kerstin U. Ludwig, Darina Czamara, Beate St Pourcain, William Brandler, Ferenc Honbolygó, Dénes Tóth, Valéria Csépe, Guillaume Huguet, Andrew P. Morris, Jacqueline Hulslander, Erik G. Willcutt, John C. DeFries, Richard K. Olson, Shelley D. Smith, Bruce F. Pennington, Anniek Vaessen, Urs Maurer, Heikki Lyytinen, Myriam Peyrard-Janvid, Paavo H. T. Leppänen, Daniel Brandeis, Milene Bonte, John F. Stein, Joel B. Talcott, Fabien Fauchereau, Arndt Wilcke, Clyde Francks, Thomas Bourgeron, Anthony P. Monaco, Franck Ramus, Karin Landerl, Juha Kere, Thomas S. Scerri, Silvia Paracchini, Simon E. Fisher, Johannes Schumacher, Markus M. Nöthen, Bertram Müller-Myhsok, and Gerd Schulte-Körne

Provenance

Received from CHORUS

File Format

application/pdf

Language

English (eng)

Extent

15 pgs

File Size

1.5 MB

Publication Statement

Copyright is held by the authors. User is responsible for all copyright compliance. This article was originally published as:

Gialluisi, A., Andlauer, T.F.M., Mirza-Schreiber, N., Moll, K., Becker, J., Hoffmann, P.,... , & Schulte-Köme. (2019). Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia. Translational Psychiatry, 9, 77. https://doi.org/10.1038/s41398-019-0402-0

Publication Title

Translational Psychiatry

Volume

9

First Page

77

ISSN

2158-3188

PubMed ID

30741946

Recommended Citation

Gialluisi, Alessandro; Andlauer, Till F. M.; Mirza-Schreiber, Nazanin; Moll, Kristina; Becker, Jessica; Hoffmann, Per; Ludwig, Kerstin U.; Czamara, Darina; St Pourcain, Beate; Brandler, William; Honbolygó, Ferenc; Tóth, Dénes; Csépe, Valéria; Huguet, Guillaume; Morris, Andrew P.; Hulslander, Jacqueline; Willcutt, Erik G.; DeFries, John C.; Olson, Richard K.; Smith, Shelley D.; Pennington, Bruce F.; Vaessen, Anniek; Maurer, Urs; Lyytinen, Heikki; Peyrard-Janvid, Myriam; Leppänen, Paavo H. T.; Brandeis, Daniel; Bonte, Milene; Stein, John F.; Talcott, Joel B.; Fauchereau, Fabien; Wilcke, Arndt; Francks, Clyde; Bourgeron, Thomas; Monaco, Anthony P.; Ramus, Franck; Landerl, Karin; Kere, Juha; Scerri, Thomas S.; Paracchini, Silvia; Fisher, Simon E.; Schumacher, Johannes; Nöthen, Markus M.; Müller-Myhsok, Bertram; and Schulte-Körne, Gerd, "Genome-Wide Association Scan Identifies New Variants Associated with a Cognitive Predictor of Dyslexia" (2019). Psychology: Faculty Scholarship. 139.
https://digitalcommons.du.edu/psychology_faculty/139 https://doi.org/10.1038/s41398-019-0402-0

DOI Link

https://doi.org/10.1038/s41398-019-0402-0