"We have produced the largest genetic study of dyslexia to date," write the study authors, led by University of Edinburgh molecular geneticist Hayley Mountford.
Dyslexia is a neurodevelopmental brain difference that can make certain aspects of modern life challenging. In the current study, participants had challenges reading and/or writing, although that is not the case in all people with dyslexia; some find other aspects of verbal processing more challenging than their peers, such as spelling and grammar, or following verbal instructions.
As with the other neurodivergences, like autism or ADHD, dyslexia comes with advantages as well, such as higher non-verbal creativity.
Past twin studies have suggested that genes strongly determine dyslexia, so Mountford and colleagues took up the challenge of pinpointing what those genetic associations are.
Their genome-wide study identified 80 regions associated with dyslexia, including 36 regions not previously reported as significant. Thirteen of these regions were novel to science, with no prior link to dyslexia.
Many of the newly associated genes are involved in early brain development. And, as expected, some of them are shared with ADHD, which can often occur alongside dyslexia.
In the vast datasets, the researchers also found correlations between dyslexia and measures of chronic pain.
"The underlying mechanism remains unelucidated, however, the genetic overlap between pain-related phenotypes and neurodevelopmental traits may hint at a shared biological basis," Mountford and team write in their paper.
With these newly identified gene associations, researchers might finally start unraveling these connections.
This research was published in Translational Psychiatry.
Tessa Koumoundouros
https://www.sciencealert.com/largest-study-of-its-kind-reveals-the-genes-behind-dyslexia
Mountford, H.S., Eising, E., Fontanillas, P. et al. Multivariate genome-wide association analysis of dyslexia and quantitative reading skill improves gene discovery. Transl Psychiatry 15, 289 (2025). https://doi.org/10.1038/s41398-025-03514-0
Abstract
The ability to read is an important life skill and a major route to education. Dyslexia, characterized by difficulties with accurate/ fluent word reading, and poor spelling is influenced by genetic variation, with a twin study heritability estimate of 0.4–0.6. Until recently, genomic investigations were limited by modest sample size. We used a multivariate genome-wide association study (GWAS) method, MTAG, to leverage summary statistics from two independent GWAS efforts, boosting power for analyses of dyslexia; the GenLang meta-analysis of word reading (N = 27,180) and the 23andMe, Inc., study of dyslexia (Ncases = 51,800, Ncontrols = 1,087,070). We increased the effective sample size to 1,228,832 participants, representing the largest genetic study of reading-related phenotypes to date. Our analyses identified 80 independent genome-wide significant loci, including 36 regions which were not previously reported as significant. Of these 36 loci, 13 were novel regions with no prior association with dyslexia. We observed clear genetic correlations with cognitive and educational measures. Gene-set analyses revealed significant enrichment of dyslexia-associated genes in four neuronal biological process pathways, and findings were further supported by enrichment of neuronally expressed genes in the developing embryonic brain. Polygenic index analysis of our multivariate results predicted between 2.34–4.73% of variance in reading traits in an independent sample, the National Child Development Study cohort (N = 6410). Polygenic adaptation was examined using a large panel of ancient genomes spanning the last ~15 k years. We did not find evidence of selection, suggesting that dyslexia has not been subject to recent selection pressure in Europeans. By combining existing datasets to improve statistical power, these results provide novel insights into the biology of dyslexia.
Doust, C., Fontanillas, P., Eising, E. et al. Discovery of 42 genome-wide significant loci associated with dyslexia. Nat Genet 54, 1621–1629 (2022). https://doi.org/10.1038/s41588-022-01192-y
Abstract
Reading and writing are crucial life skills but roughly one in ten children are affected by dyslexia, which can persist into adulthood. Family studies of dyslexia suggest heritability up to 70%, yet few convincing genetic markers have been found. Here we performed a genome-wide association study of 51,800 adults self-reporting a dyslexia diagnosis and 1,087,070 controls and identified 42 independent genome-wide significant loci: 15 in genes linked to cognitive ability/educational attainment, and 27 new and potentially more specific to dyslexia. We validated 23 loci (13 new) in independent cohorts of Chinese and European ancestry. Genetic etiology of dyslexia was similar between sexes, and genetic covariance with many traits was found, including ambidexterity, but not neuroanatomical measures of language-related circuitry. Dyslexia polygenic scores explained up to 6% of variance in reading traits, and might in future contribute to earlier identification and remediation of dyslexia.
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