Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia
Alessandro Gialluisi
(1, 2, 3)
,
Till F. M. Andlauer
(1, 2, 4)
,
Nazanin Mirza-Schreiber
(1, 5)
,
Kristina Moll
(6)
,
Jessica Becker
(7)
,
Per Hoffmann
(7)
,
Kerstin U. Ludwig
(7)
,
Darina Czamara
(1)
,
Beate St Pourcain
(8, 9, 10)
,
Ferenc Honbolygó
(11)
,
Dénes Tóth
(11)
,
Valéria Csépe
(11)
,
Guillaume Huguet
(12)
,
Yves Chaix
(13, 14)
,
Stephanie Iannuzzi
(14)
,
Jean-Francois Demonet
(15)
,
Andrew P. Morris
(16, 17, 18)
,
Jacqueline Hulslander
(19)
,
Erik G. Willcutt
(19)
,
John C. Defries
(19)
,
Richard K. Olson
(19)
,
Shelley D. Smith
(20)
,
Bruce F. Pennington
(21)
,
Anniek Vaessen
(22)
,
Urs Maurer
(23)
,
Heikki Lyytinen
(24)
,
Myriam Peyrard-Janvid
(25)
,
Paavo H. T. Leppänen
(24)
,
Daniel Brandeis
(26, 27, 28)
,
Milene Bonte
(22)
,
John F. Stein
(18)
,
Joel B. Talcott
(29)
,
Fabien Fauchereau
(12)
,
Arndt Wilcke
(30)
,
Holger Kirsten
(30, 31)
,
Bent Müller
(30)
,
Clyde Francks
(8, 9)
,
Thomas Bourgeron
(12)
,
Anthony P. Monaco
(18, 32)
,
Franck Ramus
(33)
,
Karin Landerl
(34)
,
Juha Kere
(25, 35)
,
Thomas S. Scerri
(18, 36)
,
Silvia Paracchini
(37)
,
Simon E. Fisher
(8, 9)
,
Johannes Schumacher
(7)
,
Markus M. Nöthen
(7)
,
Bertram Müller-Myhsok
(1, 2, 16)
,
Gerd Schulte-Körne
(6)
1
Max-Planck-Institut für Psychiatrie
2 SyNergy - Munich Cluster for systems neurology [Munich]
3 NEUROMED I.R.C.C.S. - Istituto Neurologico Mediterraneo
4 TUM - Technische Universität Munchen - Technical University Munich - Université Technique de Munich
5 Helmholtz Zentrum München = German Research Center for Environmental Health
6 LMU - Ludwig Maximilian University [Munich] = Ludwig Maximilians Universität München
7 Universität Bonn = University of Bonn
8 Max Planck Institute for Psycholinguistics
9 Radboud University [Nijmegen]
10 University of Bristol [Bristol]
11 MTA - Hungarian Academy of Sciences
12 GHFC (UMR_3571 / U-Pasteur_1) - Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions
13 ToNIC - Toulouse NeuroImaging Center
14 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
15 UNIL - Université de Lausanne = University of Lausanne
16 University of Liverpool
17 University of Manchester [Manchester]
18 University of Oxford
19 University of Colorado [Boulder]
20 University of Nebraska Medical Center
21 University of Denver
22 Maastricht University [Maastricht]
23 CUHK - The Chinese University of Hong Kong [Hong Kong]
24 JYU - University of Jyväskylä
25 Karolinska Institutet [Stockholm]
26 UZH - Universität Zürich [Zürich] = University of Zurich
27 ETH Zürich - Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich]
28 Universität Heidelberg [Heidelberg] = Heidelberg University
29 Aston University [Birmingham]
30 Fraunhofer IZI - Fraunhofer Institute for Cell Therapy and Immunology
31 Leipzig University / Universität Leipzig
32 Tufts University [Medford]
33 LSCP - Laboratoire de sciences cognitives et psycholinguistique
34 BioTechMed-Graz
35 Helsingin yliopisto = Helsingfors universitet = University of Helsinki
36 University of Melbourne
37 University of St Andrews [Scotland]
2 SyNergy - Munich Cluster for systems neurology [Munich]
3 NEUROMED I.R.C.C.S. - Istituto Neurologico Mediterraneo
4 TUM - Technische Universität Munchen - Technical University Munich - Université Technique de Munich
5 Helmholtz Zentrum München = German Research Center for Environmental Health
6 LMU - Ludwig Maximilian University [Munich] = Ludwig Maximilians Universität München
7 Universität Bonn = University of Bonn
8 Max Planck Institute for Psycholinguistics
9 Radboud University [Nijmegen]
10 University of Bristol [Bristol]
11 MTA - Hungarian Academy of Sciences
12 GHFC (UMR_3571 / U-Pasteur_1) - Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions
13 ToNIC - Toulouse NeuroImaging Center
14 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
15 UNIL - Université de Lausanne = University of Lausanne
16 University of Liverpool
17 University of Manchester [Manchester]
18 University of Oxford
19 University of Colorado [Boulder]
20 University of Nebraska Medical Center
21 University of Denver
22 Maastricht University [Maastricht]
23 CUHK - The Chinese University of Hong Kong [Hong Kong]
24 JYU - University of Jyväskylä
25 Karolinska Institutet [Stockholm]
26 UZH - Universität Zürich [Zürich] = University of Zurich
27 ETH Zürich - Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich]
28 Universität Heidelberg [Heidelberg] = Heidelberg University
29 Aston University [Birmingham]
30 Fraunhofer IZI - Fraunhofer Institute for Cell Therapy and Immunology
31 Leipzig University / Universität Leipzig
32 Tufts University [Medford]
33 LSCP - Laboratoire de sciences cognitives et psycholinguistique
34 BioTechMed-Graz
35 Helsingin yliopisto = Helsingfors universitet = University of Helsinki
36 University of Melbourne
37 University of St Andrews [Scotland]
Darina Czamara
- Fonction : Auteur
- PersonId : 764411
- ORCID : 0000-0001-7381-904X
Guillaume Huguet
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- PersonId : 768721
- ORCID : 0000-0002-4746-6030
Thomas Bourgeron
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- IdHAL : thomas-bourgeron
- ORCID : 0000-0001-8164-9220
- IdRef : 119761955
Franck Ramus
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- IdHAL : franck-ramus
- ORCID : 0000-0002-1122-5913
- IdRef : 071517383
Bertram Müller-Myhsok
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Gerd Schulte-Körne
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Résumé
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.
Domaines
Sciences cognitives
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