Genetics of Dyslexia

Abstract

Dyslexia is a common disorder of reading and spelling which can negatively affect the development and attainment of school‐aged children, with deficits emerging in early childhood and persisting into adulthood. The unstable definition of dyslexia poses challenges for identifying dyslexia and for research. Family studies show a familial aggregation of dyslexia, with twin studies estimating the heritability (the proportion of total variance due to genes) at around 40–60%. Genetic linkage and association methods focussing on high‐risk families led the way in genetic research aiming to localise chromosomal regions and candidate genes associated with dyslexia, although with mixed success. Genome‐wide association studies have recently made important genetic discoveries in dyslexia, revealing its polygenic nature and identifying genes and biological pathways, many of which were successfully replicated in independent samples. The potential to construct polygenic scores that predict the development of dyslexia may offer a new route for earlier and more refined diagnosis in future. Key Concepts Dyslexia is a neurodevelopmental condition characterised by a specific difficulty with reading and spelling. Original classification of dyslexia based on a discrepancy between reading skills and general cognitive ability no longer applies. Dyslexia tends to run in families with substantial familial transmission due to genes (40–80% of the population variance is genetic). Early molecular studies of dyslexia focussed on families using linkage analysis to localise chromosomal regions of interest. Candidate gene studies were mostly directed to linkage regions testing the association of variants within these regions. Replication of linkage and candidate gene study results were inconsistent between studies. Genome‐wide association studies (GWAS) of dyslexia cases versus controls have now produced reliable findings. In the largest GWAS, 42 independent single nucleotide polymorphisms were found with many replicated across different languages. Genetic correlations between dyslexia and cognitive, socio‐educational and health traits were significant, particularly attention deficit hyperactivity disorder. A polygenic score constructed from the dyslexia GWAS results robustly predicts variation in reading and spelling skills.