Largest-ever genetics study reveals hidden cause of Dyslexia

Reading determines almost all aspects of everyday life. Reading allows you to learn in school, to read signs, to read books, and talk to people. But for millions, reading is a constant struggle. Dyslexia, a common learning difference, affects about 5 to 10 percent of the population worldwide, making it harder to read words right or easily and often making spelling and writing challenging.

Researchers have long known that genetics play a role in dyslexia, but exactly which genes are implicated—and to what extent—had been much murkier. That picture now clarified because of the largest study ever conducted on reading and dyslexia.

Researchers at the University of Edinburgh, the Max Planck Institute for Psycholinguistics, and various collaborating institutions set out to map the genetic roots of reading disability. By combining the findings of two vast sets—the GenLang Consortium's reading ability tests and genetic information from more than 50,000 people who self-reported dyslexia through 23andMe—they built an unprecedented sample of more than 1.2 million participants.

Hayley Mountford, molecular geneticist at Edinburgh's School of Psychology and lead author, described why this step was so effective. "While earlier research had uncovered some genetic links, dyslexia research is still lagging far behind that into conditions like autism or attention deficit hyperactivity disorder (ADHD), and the underlying biological mechanisms were unclear," she reported to The Brighter Side of News. “The recent availability of summary statistics from two large genome-wide association studies allowed us to combine them in a more powerful meta-analysis.”

Using a method called multi-trait analysis of genome-wide association studies, or MTAG, the team was able to identify genetic regions linked to both dyslexia and reading ability, boosting their power to detect subtle signals that smaller studies had missed.

The results were sensational. Researchers identified 80 specific regions of the genome associated with dyslexia, of which 36 had not been emphasized before. Thirteen of them were novel to science, never before associated with reading traits. Some of the most significant were in genes like PPP2R3A, CSE1L, and regions close to PTPA and IER5L.

Reading ability was also researched alone and identified 35 areas that were statistically significant genetically. Most of them coincided with the dyslexia results, and this is consistent with the belief that reading ability and dyslexia are not totally different and are on a continuum. One such common indicator was from the HTT gene, well known in other neurological illnesses, as it arose unexpectedly linked to reading.

Uncovering genetic regions is just half the story. The team dug deeper to determine what these genes do and where they are expressed. Several were found to play significant roles in brain development, particularly in regions such as the cerebellum and frontal cortex. A few genes exhibited very high levels of activity during synapse synthesis, the communication crosses between neurons that facilitate information flow.

Even more convincingly, some genes were activated early during embryonic development. GABAergic neurons, astrocytes, and oligodendrocyte precursors appeared especially active. That means that infinitesimal genetic variations during brain development many years before birth can influence how reading proficiency manifests years later.

The researchers also wanted to know how much of the risk of dyslexia is explained by common genetic variation. By comparing heritability, they put the proportion of probability of developing dyslexia explained by the genetic variation in their study at 13-20 percent.

That is a large number, and it's also a reminder that most of the risk is elsewhere in untested genetic influences or environmental influences like education, access to reading help, and literacy at home. Genes do play a role, but they are not destiny.

One of the most astonishing aspects of the research was how the genetic roots of dyslexia intersect with other disorders. Of nearly 3,000 traits examined, approximately 500 had significant genetic correlations.

The strongest genetic overlaps for dyslexia were negative in that variations increasing risk for dyslexia were also linked to lower performance on some measures of intelligence, fewer schooled years, and less likelihood of earning a college degree.

More significant correlations were reported for ADHD, chronic pain, mood swings, depression, and workplace hazard exposure. Interestingly, autism spectrum disorder did not have any robust genetic linkage in this investigation, which has made it clearer what features are biologically associated with dyslexia and what features are not.

The work even detected a relationship with chronic pain. While the biological basis is unknown, Mountford and coauthors report that the overlap implies a common origin that could be explored further.

To determine whether their results held promise for application in the real world, the team built what is known as a polygenic index—a score calculated from many genetic variants that forecasts an individual's risk of dyslexia.

When tested against a test sample of over 6,000 children, the index explained up to 4.7 percent of the difference in reading capacity. That may not seem like a lot, but it is a promising start toward developing measures that potentially could screen for children at risk sooner so that schools and families can step in with targeted assistance before reading problems become habitual.

The researchers also inquired whether these variants had been shaped by evolution. Reading, after all, is a very recent human development. Using ancient DNA from people who lived up to 15,000 years ago, the researchers found no indication that dyslexia-associated variants were strongly selected for or weeded out over time. That makes sense—language may be old, but reading only came into human culture within the last few thousand years.

The research is an advance beyond understanding the biological roots of dyslexia. It also points out how much remains uncertain. Only a fraction of the risk is explained by the genetic regions identified, and the polygenic score has limited ability for individuals. Perhaps most importantly, the study drew mostly on people of European descent, so that future research must include participation to render results universal.

However, the study's size and scope create grounds for further progress. Mountford and others plan to study the overlap of genes that predispose to dyslexia with genes for ADHD, language disorders, and other diseases. They will also study the effect of genetic risk on life outcomes such as education, occupation, and mental health.

We also plan to enhance polygenic scores through the employment of more representative samples and the inclusion of environmental factors like early education and home literacy environment," Mountford said. "Finally, we plan to study how the genes identified influence brain development using cellular models and imaging genetics."

For students, families, and educators, the message is clear: dyslexia has a strong biological basis, but genes do not set anyone's destiny. Early recognition, supportive instruction, and understanding by teachers can help significantly. In the future, genetic information can allow for earlier detection of risk children, putting them into service before reading difficulties become demoralizing.

For scholars, the paper offers new directions to think about how brain development, gene expression, and environmental support interact to shape reading. Greater insight into these dynamics may one day put an end to stigma, optimize education methods, and improve lives for dyslexics everywhere.

Research findings are available online in the journal Translational Psychiatry.

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