Show simple item record

Files in this item

Thumbnail

Item metadata

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.authorHoffman, Per
dc.contributor.authorLudwig, Krestin U
dc.contributor.authorCzamara, Darina
dc.contributor.authorSt Pourcain, Beate
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.date.accessioned2020-10-15T15:30:09Z
dc.date.available2020-10-15T15:30:09Z
dc.date.issued2020-10-14
dc.identifier.citationGialluisi , A , Andlauer , T F M , Mirza-Schreiber , N , Moll , K , Becker , J , Hoffman , P , Ludwig , K U , Czamara , D , St Pourcain , B , Honbolygó , F , Tóth , D , Csépe , V , Huguet , G , Chaix , Y , Iannuzzi , S , Demonet , J-F , Morris , A P , Hulslander , J , Willcutt , E G , DeFries , J C , Olson , R K , Smith , S D , Pennington , B F , Vaessen , A , Maurer , U , Lyytinen , H , Peyrard-Janvid , M , Leppänen , P H T , Brandeis , D , Bonte , M , Stein , J F , Talcott , J B , Fauchereau , F , Wilcke , A , Kirsten , H , Müller , B , Francks , C , Bourgeron , T , Monaco , A P , Ramus , F , Landerl , K , Kere , J , Scerri , T S , Paracchini , S , Fisher , S E , Schumacher , J , Nöthen , M M , Müller-Myhsok , B & Schulte-Körne , G 2020 , ' Genome Wide Association Study reveals new insights into the heritability and genetic correlates of developmental dyslexia ' , Molecular Psychiatry . https://doi.org/10.1038/s41380-020-00898-xen
dc.identifier.issn1359-4184
dc.identifier.otherPURE: 269226013
dc.identifier.otherPURE UUID: be047dd1-4235-448f-ba0f-9041d4ebdf5e
dc.identifier.otherORCID: /0000-0001-9934-8602/work/82179937
dc.identifier.otherWOS: 000577244500002
dc.identifier.otherScopus: 85092500860
dc.identifier.urihttp://hdl.handle.net/10023/20788
dc.descriptionFunding: AG and TFMA were supported by the Munich Cluster for Systems Neurology (SyNergy). AG 535 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-542 0017 IEC, ANR-10-IDEX-0001-02 PSL, ANR-11-BSV4-014-01), European Commission (LSHM-CT-2005-018696). TFMA was supported by the BMBF 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).en
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.
dc.format.extent14
dc.language.isoeng
dc.relation.ispartofMolecular Psychiatryen
dc.rightsCopyright © The Author(s) 2020. Open Access. 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/.en
dc.subjectDevelopmental dyslexiaen
dc.subjectGWASen
dc.subjectReadingen
dc.subjectGeneticsen
dc.subjectHeritabilityen
dc.subjectPolygenic risken
dc.subjectSchizophreniaen
dc.subjectADHDen
dc.subjectBipolar disorderen
dc.subjectEducational attaintmenten
dc.subjectIntelligenceen
dc.subjectBrain cortical thicknessen
dc.subjectTransverse temporal gyrusen
dc.subjectQH426 Geneticsen
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.subjectNDASen
dc.subjectBDCen
dc.subject.lccQH426en
dc.subject.lccRC0321en
dc.titleGenome Wide Association Study reveals new insights into the heritability and genetic correlates of developmental dyslexiaen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.contributor.institutionUniversity of St Andrews.Centre for Biophotonicsen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews.Cellular Medicine Divisionen
dc.identifier.doihttps://doi.org/10.1038/s41380-020-00898-x
dc.description.statusPeer revieweden


This item appears in the following Collection(s)

Show simple item record