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

Medientyp: E-Artikel
Titel: Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia
Beteiligte: 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; [...]
Erschienen: Springer Science and Business Media LLC, 2021
Erschienen in: Molecular Psychiatry
Sprache: Englisch
DOI: 10.1038/s41380-020-00898-x
ISSN: 1359-4184; 1476-5578
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Beschreibung: <jats:title>Abstract</jats:title><jats:p>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 (<jats:italic>p</jats:italic> < 2.8 × 10<jats:sup>−6</jats:sup>) enrichment of associations at the gene level, for<jats:italic>LOC388780</jats:italic>(20p13; uncharacterized gene), and for<jats:italic>VEPH1</jats:italic>(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<jats:italic>p</jats:italic><jats:sub><jats:italic>T</jats:italic></jats:sub> = 0.05 in the training GWAS: OR = 1.23[1.16; 1.30] per standard deviation increase;<jats:italic>p</jats:italic> = 8 × 10<jats:sup>−13</jats:sup>), bipolar disorder (1.53[1.44; 1.63];<jats:italic>p</jats:italic> = 1 × 10<jats:sup>−43</jats:sup>), schizophrenia (1.36[1.28; 1.45];<jats:italic>p</jats:italic> = 4 × 10<jats:sup>−22</jats:sup>), psychiatric cross-disorder susceptibility (1.23[1.16; 1.30];<jats:italic>p</jats:italic> = 3 × 10<jats:sup>−12</jats:sup>), cortical thickness of the transverse temporal gyrus (0.90[0.86; 0.96];<jats:italic>p</jats:italic> = 5 × 10<jats:sup>−4</jats:sup>), educational attainment (0.86[0.82; 0.91];<jats:italic>p</jats:italic> = 2 × 10<jats:sup>−7</jats:sup>), and intelligence (0.72[0.68; 0.76];<jats:italic>p</jats:italic> = 9 × 10<jats:sup>−29</jats:sup>). 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.</jats:p>

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