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Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia
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Gialluisi, Alessandro; Andlauer, Till,; Mirza-Schreiber, Nazanin; Moll, Kristina; Becker, Jessica; Hoffmann, Per; Ludwig, Kerstin,; Czamara, Darina; Pourcain, Beate St; Honbolygó, Ferenc; Tóth, Dénes; Csépe, Valéria; Huguet, Guillaume; Chaix, Yves; Iannuzzi, Stephanie; Demonet, Jean-Francois; Morris, Andrew,; Hulslander, Jacqueline; Willcutt, Erik,; DeFries, John,; Olson, Richard,; Smith, Shelley,; Pennington, Bruce,; Vaessen, Anniek; Maurer, Urs; Lyytinen, Heikki; Peyrard-Janvid, Myriam; Leppänen, Paavo,; Brandeis, Daniel; Bonte, Milene; Stein, John,; Talcott, Joel,; Fauchereau, Fabien; Wilcke, Arndt; Kirsten, Holger; Müller, Bent; Francks, Clyde; Bourgeron, Thomas; Monaco, Anthony,; Ramus, Franck; Landerl, Karin; Kere, Juha; Scerri, Thomas,; Paracchini, Silvia; Fisher, Simon,; Schumacher, Johannes; Nöthen, Markus,; Müller-Myhsok, Bertram; Schulte-Körne, Gerd
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In: ISSN: 1359-4184 ; EISSN: 1476-5578 ; Molecular Psychiatry ; https://hal.archives-ouvertes.fr/hal-02976104 ; Molecular Psychiatry, Nature Publishing Group, 2020, ⟨10.1038/s41380-020-00898-x⟩ (2020)
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Abstract:
International audience ; 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.
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Keyword:
[SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences
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URL: https://hal.archives-ouvertes.fr/hal-02976104/file/MolPsy20.pdf https://hal.archives-ouvertes.fr/hal-02976104/document https://doi.org/10.1038/s41380-020-00898-x https://hal.archives-ouvertes.fr/hal-02976104
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Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia
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In: ISSN: 2158-3188 ; EISSN: 2158-3188 ; Translational Psychiatry ; https://hal.archives-ouvertes.fr/hal-02158502 ; Translational Psychiatry, Nature Pub. Group, 2019, 9, pp.77. ⟨10.1038/s41398-019-0402-0⟩ (2019)
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Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia ...
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Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia
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In: Translational Psychiatry, 9 (1) (2019)
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Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia
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Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia
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Novel genetic loci associated with hippocampal volume
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In: ISSN: 2041-1723 ; EISSN: 2041-1723 ; Nature Communications ; https://hal.archives-ouvertes.fr/hal-01488337 ; Nature Communications, Nature Publishing Group, 2017, 8, pp.13624. ⟨10.1038/ncomms13624⟩ (2017)
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Novel genetic loci underlying human intracranial volume identified through genome-wide association
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In: ISSN: 1097-6256 ; EISSN: 1546-1726 ; Nature Neuroscience ; https://hal.archives-ouvertes.fr/hal-01382716 ; Nature Neuroscience, Nature Publishing Group, 2016, 19 (12), pp.1569-1582. ⟨10.1038/nn.4398⟩ (2016)
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Common genetic variants influence human subcortical brain structures.
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In: ISSN: 0028-0836 ; EISSN: 1476-4679 ; Nature ; https://hal.archives-ouvertes.fr/hal-01196805 ; Nature, Nature Publishing Group, 2015, 520 (7546), pp.224-9. ⟨10.1038/nature14101⟩ (2015)
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Genetic analysis of dyslexia candidate genes in the European cross-linguistic NeuroDys cohort
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The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data
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In: ISSN: 1931-7557 ; EISSN: 1931-7565 ; Brain imaging and behavior (Brain Imaging Behav) ; https://hal-pasteur.archives-ouvertes.fr/pasteur-01967166 ; Brain imaging and behavior (Brain Imaging Behav), Secaucus, NJ : Springer, 2014, 8 (2), pp.152-182. ⟨10.1007/s11682-013-9269-5⟩ (2014)
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Genetic analysis of dyslexia candidate genes in the European cross-linguistic NeuroDys cohort
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Genetic analysis of dyslexia candidate genes in the European cross-linguistic NeuroDys cohort
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Genetic analysis of dyslexia candidate genes in the European cross-linguistic NeuroDys cohort
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Predictors of developmental dyslexia in European orthographies with varying complexity.
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In: ISSN: 0021-9630 ; EISSN: 1469-7610 ; Journal of Child Psychology and Psychiatry ; https://hal.archives-ouvertes.fr/hal-00965034 ; Journal of Child Psychology and Psychiatry, Wiley, 2013, 54 (6), pp.686-94. ⟨10.1111/jcpp.12029⟩ (2013)
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Genetic analysis of dyslexia candidate genes in the European cross-linguistic NeuroDys cohort.
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In: ISSN: 1018-4813 ; EISSN: 1476-5438 ; European Journal of Human Genetics ; https://hal.archives-ouvertes.fr/hal-00964958 ; European Journal of Human Genetics, Nature Publishing Group, 2013, epub ahead of print. ⟨10.1038/ejhg.2013.199⟩ (2013)
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Evidence for the late MMN as a neurophysiological endophenotype for dyslexia.
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In: PLOS ONE (2012)
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Evidence for the late MMN as a neurophysiological endophenotype for dyslexia. ...
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Evidence for the Late MMN as a Neurophysiological Endophenotype for Dyslexia
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