ABSTRACT
Reading disability is a complex neurodevelopmental disorder that is characterized by difficulties in reading despite educational opportunity and normal intelligence. Rapid automatized naming (RAN) and rapid alternating stimulus (RAS) are reliable predictors of reading outcome and involve the integration of different neural and cognitive processes required in a mature reading brain. Most studies examining the genetic basis of RAN and RAS have focused on pedigree-based analyses in samples of European descent, with limited representation of groups with Hispanic or African ancestry. In the present study, we conducted a multivariate genome-wide association analysis to identify shared genetic factors that contribute to performance across RAN Objects, RAN Letters, and RAS Letters/Numbers in a sample of Hispanic and African American youth. We then tested whether they also contribute to variance in reading fluency and word reading. Genome-wide significant, pleiotropic, effects across RAN Objects, RAN Letters, and RAS Letters/Numbers were observed for SNPs located on chromosome 10q23.31, which also showed significant association with reading fluency and word reading performance. Bioinformatic analysis of this region using extant epigenetic data from the NIH Roadmap Epigenomics Mapping Consortium indicates functionality in the brain. Neuroimaging genetic analysis showed that rs1555839, the top associated SNP, was also associated with cortical volume in the right inferior parietal cortex—a region of the brain that processes numerical information and that is activated in reading disabled individuals performing reading tasks. This study provides support for a novel locus on chromosome 10q23.31 associated with RAN, RAS, and reading-related performance.
AUTHOR SUMMARY Reading disability has a strong genetic component that is explained by multiple genes and genetic factors. The complex genetic architecture along with diverse cognitive impairments associated with reading disability, poses challenges in identifying novel genes and variants that confer risk. One method to parse out genetic and neurobiological mechanisms that contribute to reading disability is to take advantage of the high correlation among reading-related cognitive traits like rapid automatized naming (RAN) and rapid alternating stimulus (RAS) to identify shared genetic factors that contribute to common biological mechanisms. In the present study, we used a multivariate genome-wide analysis approach that identified a region of chromosome 10q23.31 associated with variation in RAN Objects, RAN Letters, and RAS Letters/Numbers performance in a sample of Hispanic and African American youth. Genetic variants in this region were also associated with reading fluency and differences in brain structures implicated in reading disability. The gene, RNLS, is located within the implicated region of chromosome 10q23.31 and plays a role in breaking down a class of chemical messengers known to affect attention, learning, and memory in the brain. These findings provide a basis to inform our understanding of the biological basis of reading disability.