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Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia

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Author(s)

Alessandro Gialluisi, Till F. M. Andlauer, Nazanin Mirza-schreiber, Kristina Moll, Jessica Becker, Per Hoffmann, 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 & 25 more 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, Gerd Schulte-körne

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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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Details

Original languageEnglish
Article number77
Number of pages15
JournalTranslational Psychiatry
Volume9
Early online date11 Feb 2019
DOIs
Publication statusE-pub ahead of print - 11 Feb 2019

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