TY - JOUR
T1 - Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia
AU - Gialluisi, Alessandro
AU - Andlauer, Till F.M.
AU - Mirza-Schreiber, Nazanin
AU - Moll, Kristina
AU - Becker, Jessica
AU - Hoffmann, Per
AU - Ludwig, Kerstin U.
AU - Czamara, Darina
AU - Pourcain, Beate St
AU - Honbolygó, Ferenc
AU - Tóth, Dénes
AU - Csépe, Valéria
AU - Huguet, Guillaume
AU - Chaix, Yves
AU - Iannuzzi, Stephanie
AU - Demonet, Jean Francois
AU - Morris, Andrew P.
AU - Hulslander, Jacqueline
AU - Willcutt, Erik G.
AU - DeFries, John C.
AU - Olson, Richard K.
AU - Smith, Shelley D.
AU - Pennington, Bruce F.
AU - Vaessen, Anniek
AU - Maurer, Urs
AU - Lyytinen, Heikki
AU - Peyrard-Janvid, Myriam
AU - Leppänen, Paavo H.T.
AU - Brandeis, Daniel
AU - Bonte, Milene
AU - Stein, John F.
AU - Talcott, Joel B.
AU - Fauchereau, Fabien
AU - Wilcke, Arndt
AU - Kirsten, Holger
AU - Müller, Bent
AU - Francks, Clyde
AU - Bourgeron, Thomas
AU - Monaco, Anthony P.
AU - Ramus, Franck
AU - Landerl, Karin
AU - Kere, Juha
AU - Scerri, Thomas S.
AU - Paracchini, Silvia
AU - Fisher, Simon E.
AU - Schumacher, Johannes
AU - Nöthen, Markus M.
AU - Müller-Myhsok, Bertram
AU - Schulte-Körne, Gerd
N1 - 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/.
PY - 2021/7
Y1 - 2021/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85092500860&partnerID=8YFLogxK
U2 - 10.1038/s41380-020-00898-x
DO - 10.1038/s41380-020-00898-x
M3 - Article
C2 - 33057169
AN - SCOPUS:85092500860
SN - 1359-4184
VL - 26
SP - 3004
EP - 3017
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 7
ER -