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 - St Pourcain, Beate
AU - Honbolygo, Ferenc
AU - Toth, Denes
AU - Csepe, Valeria
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 - Leppanen, 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 - Mueller, 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 - Noethen, Markus M.
AU - Mueller-Myhsok, Bertram
AU - Schulte-Koerne, Gerd
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 x 10(-6)) enrichment of associations at the gene level, forLOC388780(20p13; uncharacterized gene), and forVEPH1(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 (atp(T) = 0.05 in the training GWAS: OR = 1.23[1.16; 1.30] per standard deviation increase;p = 8 x 10(-13)), bipolar disorder (1.53[1.44; 1.63];p = 1 x 10(-43)), schizophrenia (1.36[1.28; 1.45];p = 4 x 10(-22)), psychiatric cross-disorder susceptibility (1.23[1.16; 1.30];p = 3 x 10(-12)), cortical thickness of the transverse temporal gyrus (0.90[0.86; 0.96];p = 5 x 10(-4)), educational attainment (0.86[0.82; 0.91];p = 2 x 10(-7)), and intelligence (0.72[0.68; 0.76];p = 9 x 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 x 10(-6)) enrichment of associations at the gene level, forLOC388780(20p13; uncharacterized gene), and forVEPH1(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 (atp(T) = 0.05 in the training GWAS: OR = 1.23[1.16; 1.30] per standard deviation increase;p = 8 x 10(-13)), bipolar disorder (1.53[1.44; 1.63];p = 1 x 10(-43)), schizophrenia (1.36[1.28; 1.45];p = 4 x 10(-22)), psychiatric cross-disorder susceptibility (1.23[1.16; 1.30];p = 3 x 10(-12)), cortical thickness of the transverse temporal gyrus (0.90[0.86; 0.96];p = 5 x 10(-4)), educational attainment (0.86[0.82; 0.91];p = 2 x 10(-7)), and intelligence (0.72[0.68; 0.76];p = 9 x 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.
KW - READING-DISABILITY
KW - INDIVIDUAL-DIFFERENCES
KW - SUSCEPTIBILITY GENE
KW - MOLECULAR-GENETICS
KW - LANGUAGE
KW - COMORBIDITY
KW - LOCUS
KW - AGE
KW - SCHIZOPHRENIA
KW - INTELLIGENCE
U2 - 10.1038/s41380-020-00898-x
DO - 10.1038/s41380-020-00898-x
M3 - Article
C2 - 33057169
SN - 1359-4184
VL - 26
SP - 3004
EP - 3017
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 7
ER -