NEW YORK — Researchers have tied four genes to word-reading ability in a series of large genome-wide association studies of reading and language-related traits, but were unable to replicate most SNPs and genes previously tied to those skills.
Their analysis, which appeared this week in the Proceedings of the National Academy of Sciences, additionally examined the heritability and shared genetic features behind complex spoken and written language-related traits, an ability specific to humans.
"We have known for many years that individual differences in the relevant skills must be influenced by variations in our genomes," first author Else Eising from the Max Planck Institute for Psycholinguistics in Nijmegen, Netherlands, said in a statement. "This is the first time that datasets of tens of thousands of participants have been gathered together to really reliably investigate the many DNA variants that contribute."
In their analysis, researchers from the GenLang consortium examined five reading and language-related traits — word reading, nonword reading, spelling, phoneme awareness, and nonword repetition — in up to nearly 34,000 people from 22 different cohorts. These cohorts included not only native English speakers, but also native speakers of Dutch, Spanish, German, and other languages.
They uncovered one locus on chromosome 1 linked with word reading. While this locus has not been associated previously with general cognitive performance, the nearby gene DOCK7 has a role in neurogenesis, while the nearby ANGPTL3 encodes a vascular endothelium growth factor. Further, the linked locus appears to harbor an expression quantitative trait locus regulating DOCK7 and the autophagy-encoding ATG4C in the cerebellum and regulates those genes plus USP1, which encodes an enzyme involved in the Fanconi anemia pathway, in the blood. These four genes, the researchers noted, could represent candidate genes involved in word reading.
However, the researchers were unable to confirm a number of SNPs and genes that had previously been linked to reading- and language-related traits. Of the 54 candidate SNPs and 20 candidate genes the researchers examined in their dataset, they only found support for one, DCDC2, despite their larger sample size.
"We suspect that quite a few of the previously reported candidate gene associations with reading- and language-related traits in studies with small samples reflect false-positive findings," Eising said.
Building on their findings, the researchers also found a high level of genetic relatedness among the five reading- and language-related traits they analyzed. At the same time, they noted genetic overlaps with general cognitive ability, though not with the nonverbal aspect of IQ.
By adding in MRI data, the researchers additionally homed in on brain regions with genetic associations with their five reading and language-related traits. In particular, the surface area of the banks of the superior temporal sulcus of the left hemisphere, where spoken and written language are processed, shared genetic factors with reading- and language-related skills.
Though reading and writing are recent cultural advances, these skills emerged through biological evolution along the human lineage. Using their dataset, the researchers explored the genomic regions linked to reading- and language-related traits at different time scales of human evolution to find that these spots along the genome fell in stretches that were depleted for Neanderthal introgression, suggesting an intolerance to gene flow.
The researchers noted that it is challenging to conduct large-scale analysis of these traits, as they are not well captured by questionnaires.
"In the future, we hope to build on these efforts with genetically informative datasets covering a broader range of traits relevant for language, for instance including abilities related to grammatical processing," added senior author Simon Fisher, the director of the Max Planck Institute for Psycholinguistics and founder of the GenLang consortium. "To more quickly and easily characterize reading and language skills in large groups of individuals, we will likely need development of tests that can be administered online, and this is a major focus of the GenLang consortium moving forward."