Genome‐wide association study of shared components of reading disability and language impairment

Abstract

Written and verbal language are neurobehavioral traits vital to the development of communication skills. Unfortunately, disorders involving these traits—specifically reading disability (RD) and language impairment (LI)—are common and prevent affected individuals from developing adequate communication skills, leaving them at risk for adverse academic, socioeconomic, and psychiatric outcomes. Both RD and LI are complex traits that frequently co-occur, leading us to hypothesize that these disorders share genetic etiologies. To test this, we performed a genome wide association study on individuals affected with both RD and LI in the Avon Longitudinal Study of Parents and Children. The strongest associations were seen with markers in ZNF385D (OR=1.81, p=5.45 × 10−7) and COL4A2 (OR=1.71, p=7.59×10−7). Markers within NDST4 showed the strongest associations with LI individually (OR=1.827, p=1.40×10−7). We replicated association of ZNF385D using receptive vocabulary measures in the Pediatric Imaging Neurocognitive Genetics study (p=0.00245). We then used diffusion tensor imaging fiber tract volume data on 16 fiber tracts to examine the implications of replicated markers. ZNF385D was a predictor of overall fiber tract volumes in both hemispheres, as well as global brain volume. Here, we present evidence for ZNF385D as a candidate gene for RD and LI. The implication of transcription factor ZNF385D in RD and LI underscores the importance of transcriptional regulation in the development of higher order neurocognitive traits. Further study is necessary to discern target genes of ZNF385D and how it functions within neural development of fluent language.

Language development in rural and urban Russian-speaking children with and without developmental language disorder

“…DLD is a highly familial and heritable neurodevelopmental disorder (Stromswold, 1998; Tomblin, 1989), and it is now widely accepted that it has prominent genetic and neurobiological components. Little is known about the precise characteristics of these components and the mechanisms of their action, despite several intriguing molecular genetic (e.g., Eicher et al, 2013; Nudel et al, 2014) and neuroimaging (e.g., Soriano-Mas et al, 2009; Whalley et al, 2011) findings published in recent years. Perhaps surprisingly, environmental influences on language development in children with DLD have rarely been investigated.…”

Interhemispheric gene expression differences in the cerebral cortex of humans and macaque monkeys

“…Genes in this module (n=639) were not enriched in any GO category, although it contained mainly neuronal (p=2,71e-12) and nuclear genes (p=1,56e-05). Among the genes in the module, four were previously related to brain asymmetry and reading disabilities: DAZAP1 (Luciano et al, 2013), LMO4 (Sun et al, 2005), PLEKHA1 (Eicher et al, 2013) and NBEA (Medland, 2009). …”

Predicting Developmental Dyslexia: A Brief Review of Genetics, Language and the Brain

“…diagnosed when a child's language development lags behind his/her other cognitive skills despite exhibiting average or above-average nonverbal abilities [21]. In fact, a number of genes implicated in DD, DCDC2, KIAA0319, FOXP2, CNTNAP2, are also implicated in language impairment [22]. Furthermore, markers within KIAA0319, FOXP2, CNTNAP2, and ZNF385D may contribute to comorbid diagnoses of DD and language impairment [22].…”

“…In fact, a number of genes implicated in DD, DCDC2, KIAA0319, FOXP2, CNTNAP2, are also implicated in language impairment [22]. Furthermore, markers within KIAA0319, FOXP2, CNTNAP2, and ZNF385D may contribute to comorbid diagnoses of DD and language impairment [22].…”