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dc.contributor.authorGialluisi, Alessandro
dc.contributor.authorAndlauer, Till F. M.
dc.contributor.authorMirza-Schreiber, Nazanin
dc.contributor.authorMoll, Kristina
dc.contributor.authorBecker, Jessica
dc.contributor.authorHoffmann, Per
dc.contributor.authorLudwig, Kerstin U.
dc.contributor.authorCzamara, Darina
dc.contributor.authorPourcain, Beate St
dc.contributor.authorHonbolygó, Ferenc
dc.contributor.authorTóth, Dénes
dc.contributor.authorCsépe, Valéria
dc.contributor.authorHuguet, Guillaume
dc.contributor.authorChaix, Yves
dc.contributor.authorIannuzzi, Stephanie
dc.contributor.authorDemonet, Jean-Francois
dc.contributor.authorMorris, Andrew P.
dc.contributor.authorHulslander, Jacqueline
dc.contributor.authorWillcutt, Erik G.
dc.contributor.authorDeFries, John C.
dc.contributor.authorOlson, Richard K.
dc.contributor.authorSmith, Shelley D.
dc.contributor.authorPennington, Bruce F.
dc.contributor.authorVaessen, Anniek
dc.contributor.authorMaurer, Urs
dc.contributor.authorLyytinen, Heikki
dc.contributor.authorPeyrard-Janvid, Myriam
dc.contributor.authorLeppänen, Paavo H. T.
dc.contributor.authorBrandeis, Daniel
dc.contributor.authorBonte, Milene
dc.contributor.authorStein, John F.
dc.contributor.authorTalcott, Joel B.
dc.contributor.authorFauchereau, Fabien
dc.contributor.authorWilcke, Arndt
dc.contributor.authorKirsten, Holger
dc.contributor.authorMüller, Bent
dc.contributor.authorFrancks, Clyde
dc.contributor.authorBourgeron, Thomas
dc.contributor.authorMonaco, Anthony P.
dc.contributor.authorRamus, Franck
dc.contributor.authorLanderl, Karin
dc.contributor.authorKere, Juha
dc.contributor.authorScerri, Thomas S.
dc.contributor.authorParacchini, Silvia
dc.contributor.authorFisher, Simon E.
dc.contributor.authorSchumacher, Johannes
dc.contributor.authorNöthen, Markus M.
dc.contributor.authorMüller-Myhsok, Bertram
dc.contributor.authorSchulte-Körne, Gerd
dc.identifier.citationGialluisi, 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. (2020). Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia. Molecular Psychiatry, Early online. DOI: 10.1038/s41380-020-00898-x
dc.description.abstractDevelopmental 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.en
dc.publisherNature Publishing Group
dc.relation.ispartofseriesMolecular Psychiatry
dc.rightsCC BY 4.0
dc.subject.othergenetic correlates
dc.subject.otherdevelopmental dyslexia
dc.titleGenome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia
dc.contributor.laitosPsykologian laitosfi
dc.contributor.laitosDepartment of Psychologyen
dc.relation.volumeEarly online
dc.rights.copyright© The Author(s) 2020
dc.subject.ysogeneettiset tekijät
jyx.fundinginformationAG and TFMA were supported by the Munich Cluster for Systems Neurology (SyNergy). AG was supported by Fondazione Umberto Veronesi. SP is a Royal Society University Research fellow. BMM, CF, BSP and SEF are supported by the Max Planck Society. AW, BM and HK were funded by the Fraunhofer Society and the Max Planck Society within the “Pakt für Forschung und Innovation”. HK was also supported by LIFE—Leipzig Research Center for Civilization Diseases funded by means of the European Union; the European Regional Development Fund (ERDF); and the Free State of Saxony within the excellence initiative. FR is supported by Agence Nationale de la Recherche (ANR-06-NEURO-019-01, ANR-17-EURE-0017 IEC, ANR-10-IDEX-0001-02 PSL, ANR-11-BSV4-014-01), European Commission (LSHM-CT-2005-018696). TFMA was supported by the B.M.B.F. through the DIFUTURE consortium of the Medical Informatics Initiative Germany (grant 01ZZ1804A) and by the European Union’s Horizon 2020 Research and Innovation Programme (grant MultipleMS, EU RIA 733161). We would also like to acknowledge our project partners Catherine Billard, Caroline Bogliotti, Vanessa Bongiovanni, Laure Bricout, Camille Chabernaud, Isabelle Comte-Gervais, Florence Delteil-Pinton, Florence George, Christophe-Loïc Gérard, Marie Lageat, Marie-France Leheuzey, Marie-Thérèse Lenormand, Marion Liébert, Emilie Longeras, Emilie Racaud, Isabelle Soares-Boucaud, Sylviane Valdois, Nadège Villiermet, and Johannes Ziegler. This study makes use of data generated by the WTCCC. A full list of the investigators who contributed to the generation of the data is available at Funding for the WTCCC project was provided by the Wellcome Trust under awards 076113 and 085475. Open Access funding enabled and organized by Projekt DEAL.

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