In:
Molecular Psychiatry, Springer Science and Business Media LLC, Vol. 26, No. 7 ( 2021-07), p. 3004-3017
Abstract:
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 p T = 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.
Type of Medium:
Online Resource
ISSN:
1359-4184
,
1476-5578
DOI:
10.1038/s41380-020-00898-x
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2021
detail.hit.zdb_id:
1502531-7
Permalink