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

Alessandro Gialluisi , Till F M Andlauer , Nazanin Mirza-Schreiber , Kristina Moll , Jessica Becker , Per Hoffmann (1) , Kerstin U Ludwig , Darina Czamara , Beate St Pourcain , William Brandler , Ferenc Honbolygó , Dénes Tóth , Valéria Csépe , Guillaume Huguet (2, 3) , 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 (4) , Milene Bonte , John F Stein , Joel B Talcott , Fabien Fauchereau (3) , Arndt Wilcke (5) , Clyde Francks (6) , Thomas Bourgeron (3) , Anthony P. Monaco (7) , Franck Ramus (8) , Karin Landerl , Juha Kere (9) , Thomas S Scerri , Silvia Paracchini , Simon Fisher (6) , Johannes Schumacher (10) , Markus M. Nöthen (11) , Bertram Müller-Myhsok , Gerd Schulte-Körne (12)

1 Rheinische Friedrich-Wilhelms-Universität Bonn
2 UdeM - Université de Montréal
3 GHFC (UMR_3571 / U-Pasteur_1) - Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions
4 Universität Heidelberg [Heidelberg] = Heidelberg University
5 Translational Centre for Regenerative Medicine (TRM); Department of Cell Therapy
6 Donders Institute for Brain, Cognition and Behaviour
7 The Wellcome Trust Centre for Human Genetics [Oxford]
8 LSCP - Laboratoire de sciences cognitives et psycholinguistique
9 Helsingin yliopisto = Helsingfors universitet = University of Helsinki
10 Institute of Human Genetics
11 Department of Genomics, Life and Brain Center
12 Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy

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.

Domaines: Sciences cognitives; Génétique humaine

Alessandro Gialluisi, Till F M Andlauer, Nazanin Mirza-Schreiber, Kristina Moll, Jessica Becker, et al.. Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia. Translational Psychiatry, 2019, 9, pp.77. ⟨10.1038/s41398-019-0402-0⟩. ⟨hal-02158502⟩