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