A1 Journal article (refereed)
Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia (2021)
Gialluisi, A., Andlauer, T. F. M., Mirza-Schreiber, N., Moll, K., Becker, J., Hoffmann, P., Ludwig, K. U., Czamara, D., Pourcain, B. S., Honbolygó, F., Tóth, D., Csépe, V., Huguet, G., Chaix, Y., Iannuzzi, S., Demonet, J.-F., Morris, A. P., Hulslander, J., Willcutt, E. G., . . . Schulte-Körne, G. (2021). Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia. Molecular Psychiatry, 26(7), 3004-3017. https://doi.org/10.1038/s41380-020-00898-x
JYU authors or editors
Publication details
All authors or editors: 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; et al.
Journal or series: Molecular Psychiatry
ISSN: 1359-4184
eISSN: 1476-5578
Publication year: 2021
Publication date: 14/10/2020
Volume: 26
Issue number: 7
Pages range: 3004-3017
Publisher: Nature Publishing Group
Publication country: United Kingdom
Publication language: English
DOI: https://doi.org/10.1038/s41380-020-00898-x
Publication open access: Openly available
Publication channel open access: Partially open access channel
Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/72252
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.
Keywords: heredity; genetic factors; dyslexia
Free keywords: heritability; genetic correlates; developmental dyslexia
Contributing organizations
Ministry reporting: Yes
Reporting Year: 2021
JUFO rating: 3