The mediation role of reading-related endophenotypes in the gene-to-reading pathway

Although individual differences in reading-related skills are largely influenced by genetic variation, the molecular basis of the heritability of this phenotype is far from understood. Functional single-nucleotide polymorphisms spanning reading-candidate genes and genome-wide significant top hits were identified. By using a multiple-predictor/multiple-mediator framework, we investigated whether relationships between functional genetic variants (DYX1C1-rs3743205, DYX1C1-rs57809907, KIAA0319-rs9461045, and KIAA0319-Haplotype) and genome-wide significant top hits (rs11208009 on chromosome 1) and reading skills could be explained by reading-related cognitive and sensory endophenotypes in a sample of 328 8-year-old twins. The association between rs3743205 and rs57809907 with reading skills is partially mediated by phonological awareness (PA). Specifically, the rs3743205-C/C genotype and carrying the minor ‘A’ allele of rs57809907 were associated with lower PA scores which in turn was correlated with poorer reading skills. These findings reveal insights into the sequential gene-behavior cascade in reading acquisition and contribute to the growing literature on the neurogenetic machinery of reading development.