NEW YORK – An international team has started teasing out the brain structural changes that track with genetic contributors to dyslexia, a neurodevelopmental condition that affects reading, writing, and spelling and is detected in up to 7 percent of children during their school years.
"Individual dyslexia-disposing genetic variants showed distinct patterns of association with brain structure," senior and corresponding author Clyde Francks, a researcher affiliated with the Max Planck Institute for Psycholinguistics and Radboud University, and his colleagues reported in Science Advances on Wednesday, noting that specific brain networks "each had their own genomic profiles related to dyslexia susceptibility."
For their study, Francks and colleagues from the Netherlands and UK analyzed magnetic resonance imaging-based brain structure data for 35,231 genotyped adult participants in the UK Biobank project, searching for genetic ties to brain features and polygenic scores for dyslexia and related traits or conditions. For this, they used polygenic dyslexia disposition estimates based on almost 13,800 variants established in a 23andMe genome-wide association study of dyslexia that involved 51,800 cases and more than 1 million controls.
"The combination of brain features uniquely associated with dyslexia polygenic disposition is likely to distinguish liability to this particular trait among others," the authors noted. "We therefore went on to quantify the polygenic dispositions of UK Biobank individuals to [attention-deficit hyperactivity disorder], educational attainment, school grades, fluid intelligence, and the reading-related psychometric traits of single-word reading, non-word reading, spelling, and phonemic awareness."
When the team looked at brain structure associations with a dyslexia polygenic risk score, for example, it saw reduced regional volumes across several brain regions in participants with higher-than-usual PRS, along with head size differences and dyslexia PRS-related changes in apparent fiber density of their brains.
A brain-wide association study involving a subset of variants at 35 loci linked to dyslexia in the 23andMe GWAS, meanwhile, highlighted specific brain structure changes coinciding with different dyslexia-associated variants.
"The 35 brain-wide maps showed some limited convergence, most notably in a left hemisphere medial prefrontal region peaking in Brodmann area 32 that was associated with six of the variants," the authors reported, "but there was also much divergence across the 35 maps."
The team's subsequent analyses of genetic correlations between dyslexia and other traits backed up findings from prior studies, pointing to ties with educational attainment, school grades, reading ability, or ADHD. Likewise, polygenic contributors to these traits were associated with brain volume, fiber density, and other brain features assessed in the UK Biobank effort.
Together, the study "shows the utility of a complementary approach to studying the neurobiology of dyslexia, through identifying neural correlates of genetic disposition while leveraging large-scale population data to overcome statistical uncertainty," the authors explained, adding that their results "implicated diverse brain structures, notably involved in motor, language-related, and visual functions."