Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia

Abstract

Developmental dyslexia (DD) is a learning disorder affecting the ability to read, with a heritability of 40–60%. A notable part of this heritability remains unexplained, and large genetic studies are warranted to identify new susceptibility genes and clarify the genetic bases of dyslexia. We carried out a genome-wide association study (GWAS) on 2274 dyslexia cases and 6272 controls, testing associations at the single variant, gene, and pathway level, and estimating heritability using single-nucleotide polymorphism (SNP) data. We also calculated polygenic scores (PGSs) based on large-scale GWAS data for different neuropsychiatric disorders and cortical brain measures, educational attainment, and fluid intelligence, testing them for association with dyslexia status in our sample. We observed statistically significant (p < 2.8 × 10−6) enrichment of associations at the gene level, for LOC388780 (20p13; uncharacterized gene), and for VEPH1 (3q25), a gene implicated in brain development. We estimated an SNP-based heritability of 20–25% for DD, and observed significant associations of dyslexia risk with PGSs for attention deficit hyperactivity disorder (at pT = 0.05 in the training GWAS: OR = 1.23[1.16; 1.30] per standard deviation increase; p = 8 × 10−13), bipolar disorder (1.53[1.44; 1.63]; p = 1 × 10−43), schizophrenia (1.36[1.28; 1.45]; p = 4 × 10−22), psychiatric cross-disorder susceptibility (1.23[1.16; 1.30]; p = 3 × 10−12), cortical thickness of the transverse temporal gyrus (0.90[0.86; 0.96]; p = 5 × 10−4), educational attainment (0.86[0.82; 0.91]; p = 2 × 10−7), and intelligence (0.72[0.68; 0.76]; p = 9 × 10−29). This study suggests an important contribution of common genetic variants to dyslexia risk, and novel genomic overlaps with psychiatric conditions like bipolar disorder, schizophrenia, and cross-disorder susceptibility. Moreover, it revealed the presence of shared genetic foundations with a neural correlate previously implicated in dyslexia by neuroimaging evidence.

Publication DOI: https://doi.org/10.1038/s41380-020-00898-x
Divisions: College of Health & Life Sciences > School of Psychology
Additional Information: 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: Molecular Biology,Psychiatry and Mental health,Cellular and Molecular Neuroscience
Publication ISSN: 1476-5578
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2020-10-14
Published Online Date: 2020-10-14
Accepted Date: 2020-09-18
Authors: Gialluisi, Alessandro
Andlauer, Till F.M.
Mirza-Schreiber, Nazanin
Moll, Kristina
Becker, Jessica
Hoffmann, Per
Ludwig, Kerstin U.
Czamara, Darina
Pourcain, Beate St
Honbolygó, Ferenc
Tóth, Dénes
Csépe, Valéria
Huguet, Guillaume
Chaix, Yves
Iannuzzi, Stephanie
Demonet, Jean Francois
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. (ORCID Profile 0000-0001-7958-8369)
Fauchereau, Fabien
Wilcke, Arndt
Kirsten, Holger
Müller, Bent
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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