The largest genome-wide association study (GWAS) to date identified 42 independent locations in the genome associated with dyslexia. The study, conducted by scientists at the University of Edinburgh, Max Planck Institute for Psycholinguistics in the Netherlands, QIMR Berghofer Medical Research Institute in Australia and the US company 23andMe, and reported in the journal Nature Genetics on Thursday, helps us better understand the genetic underpinnings of why some children struggle to read or spell.
“Our findings show that common genetic differences have very similar effects in boys and girls, and that there is a genetic link between dyslexia and ambidexterity. Previous work suggested some brain structures may be altered in people with dyslexia, but we did not find evidence that genes explain this,” said Michelle Luciano, PhD, from the University of Edinburgh’s School of Philosophy, Psychology and Language Sciences, who is the senior author of the study. “Our results also suggest that dyslexia is very closely, genetically related to performance on reading and spelling tests reinforcing the importance of standardized testing in identifying dyslexia.”
The ability to read and write is central to education, employment, and indeed one’s socio-economic status. Yet nearly one in ten children is diagnosed with dyslexia, which can persist into adulthood if left untreated. Analyses of family histories have suggested dyslexia is predominantly inherited (up to 70%). Previous studies linking dyslexia to specific genes were conducted on a few families and the genetic markers for the condition remained unclear.
The current GWAS study was conducted on data from 51,800 adults with self-reported dyslexia diagnosis and more than a million normal people. The researchers tested the association between millions of genetic variants with dyslexia and found 42 significant variants. Fifteen of these were in genes linked to cognitive ability or educational attainment. Some of the sites were associated with neurodevelopmental conditions, such as language delay, while others overlapped with attention deficit hyperactivity disorder (ADHD) and psychiatric conditions, but 27 of the 42 sites were new and likely more specific to dyslexia.
The investigators then validated 23 of the genomic sites, including 13 new sites, through comparisons with independent datasets that included individuals of Chinese and European ancestry. They found, the expression of the dyslexia was similar in both sexes, and that dyslexia was genetically linked to other traits such as ambidexterity, but not neuroanatomical measures of language circuits. Several genetic variants associated with dyslexia were also significant in the Chinese-speaking dataset. This showed that general cognitive processes in learning to read are not dependent on a specific language.
The researchers said they were able to predict reading and spelling abilities of children and adults from four independent research datasets using the genetic information from the GWAS study, but not with the accuracy needed for diagnostic use. A polygenic risk score (PRS) estimates an individual’s genetic liability to a trait or disease and is calculated from their genotype profile and relevant GWAS data. With further studies, PRS for dyslexia calculated based on the current GWAS study could contribute to earlier detection and treatment of children with dyslexia.