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

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 non-additive, 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.