The role of READ1 and KIAA0319 genetic variations in developmental dyslexia: testing main and interactive effects

摘要

Developmental dyslexia (DD) is a complex heritable condition characterized by impaired reading abilities. Two well-replicated candidate risk factors are as follows: (1) regulatory element associated with dyslexia 1 (READ1), which is located in intron 2 of DCDC2 and acts as a binding site for protein regulation of DCDC2 expression; and (2) a three-single-nucleotide polymorphism risk haplotype spanning KIAA0319. Phylogenetically similar READ1 variants showed synergistic effects with the KIAA0319 risk haplotype on reading-related phenotypes in a general population sample. Here we examine the association between different allele classes in READ1, the KIAA0319 risk haplotype and reading-related traits in a cohort of 368 Italian children with DD and their siblings (n= 266) by testing both main and non-additive effects. We replicated the deleterious main effects upon both reading accuracy and speed exerted by the longer READ1 alleles. We further supported the interdependence through nonadditive, possibly antagonistic, effects between READ1 and the KIAA0319 risk haplotype on reading accuracy. By suggesting the presence of common biological processes underlying reading (dis) ability, these findings represent initial support for a generalist effect of the non-additive interdependence between READ1 and the KIAA0319 risk haplotype. Moreover, our results confirm that using as much information as possible about genetic interdependence among dyslexia-candidate genes can help in clinically assessing the individual risk for DD.