Bosson-Heenan, J. | Search bioRxiv

bioRxiv2019

Effect of READ1 on latent profiles of reading disability and comorbid attention and language learning disability subtypes

Recent studies of co-occurring reading disability (RD) and attention deficit/hyperactivity disorder (ADHD), and co-occurring RD and language learning disability (LLD), support a core disability plus co-occurrence model focused on language and attention. Genetic factors have been associated with poor reading performance. However, little is known about whether different genetic variants independently contribute to RD co-occurrence subtypes. We aimed to identify subgroups of struggling readers using a latent profile analysis (LPA) in a sample of 1,432 Hispanic American and African American youth. RD classes were then tested for association with variants of READ1, a regulatory element within the candidate RD risk gene, DCDC2. Six groups were identified in the LPA using RD designation as a known-class variable. The three RD classes identified groups of subjects with neurocognitive profiles representing RD+ADHD, specific phonological deficit RD, and RD+LLD. Genetic associations across RD subtypes were investigated against functional groupings of READ1. The RU1-1 group of READ1 alleles was associated with RD cases that were marked by deficits in both processing speed and attention (RD + ADHD). The DCDC2 microdeletion that encompasses READ1 was associated with RD cases showing a phonological deficit RD profile. These findings provide evidence for differential genetic contribution to RD subtypes, and that previously implicated genetic variants for RD may share an underlying genetic architecture across population groups for reading disability.

genetics↗

bioRxiv2018

Dual language experience enhances neural activation variability during an fMRI reading and language task

Previous work has shown that experience speaking more than one language in childhood is associated with decreased intra-individual neural variability in electrophysiological responses during a low-level speech perception task. However, no study has yet evaluated the impact of dual language experience on variability in fMRI responses during a higher-level spoken and written language processing task. In the current study, we calculated trial-by-trial variability in neural activation during an fMRI task that involved deciding whether spoken or printed English words matched pictures of items. We compared trial-by-trial neural activation variability between two groups of 8-15 year-old children: a group of dual language learners (N = 24; 11 female) who were Spanish-dominant and acquiring English, and a group of monolingual learners who were English-dominant (N = 17; 9 female). We found that when controlling for a variety of language, general cognitive, and demographic measures, neural activation variability for printed words was greater in the dual language learners compared to the monolingual learners in the right middle frontal gyrus, a brain region previously associated with attentional control. This finding highlights how neural variability offers a window of opportunity to examine experience-dependent mechanisms during human development, and motivates future research on bilingual language processing.

neuroscience↗

bioRxiv2017

Multivariate genome-wide association study of rapid automatized naming and rapid alternating stimulus in Hispanic and African American youth.

Reading disability is a complex neurodevelopmental disorder that is characterized by difficulties in reading despite educational opportunity and normal intelligence. Performance on rapid automatized naming (RAN) and rapid alternating stimulus (RAS) tests gives a reliable predictor of reading outcome. These tasks involve the integration of different neural and cognitive processes required in a mature reading brain. Most studies examining the genetic factors that contribute to RAN and RAS performance 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 (n=1,331). We then tested whether these factors 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 (rs1555839, multivariate association, p=2.23 x 10-8), which also showed significant association with reading fluency and word reading performance (p <0.001). Bioinformatic analysis of this region using epigenetic data from the NIH Roadmap Epigenomics Mapping Consortium indicates active transcription of the gene RNLS in the brain. Neuroimaging genetic analysis of fourteen cortical regions in an independent sample of typically developing children across multiple ethnicities (n=690) showed that rs1555839 was associated with variation in volume of the right inferior parietal cortex--a region of the brain that processes numerical information and has been implicated in reading disability. This study provides support for a novel locus on chromosome 10q23.31 associated with RAN, RAS, and reading-related performance.\n\nAUTHOR SUMMARYReading 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 begin parsing 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 1,331 Hispanic and African American youth in the Genes, Reading, and Dyslexia (GRaD) Study. Genetic variants in this region were also associated with reading fluency in GRaD, and differences in brain structures implicated in reading disability in a separate sample of 690 children. 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.

genetics↗