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

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 (2019). Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia. Translational psychiatry, 9 (1), p. 77.

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.

Publication DOI: https://doi.org/10.1038/s41398-019-0402-0
Divisions: Life & Health Sciences > Psychology
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Life & Health Sciences
Additional Information: © The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Uncontrolled Keywords: Psychiatry and Mental health,Cellular and Molecular Neuroscience,Biological Psychiatry
Full Text Link: http://www.natu ... 1398-019-0402-0
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
Published Online Date: 2019-02-11
Published Date: 2019-02-11
Authors: 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. ( 0000-0001-7958-8369)
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
Schulte-körne, Gerd

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