Associations between READ1 deletion, reading proficiency, and white matter network organisation in children with and...

Developmental dyslexia (DD) is a common neurodevelopmental disorder, whose causes lie in genetic and neurobiological underpinnings. DCDC2 is one of the most replicated candidate genes underlying the etiology of reading (dis)abilities and has been associated with neural migration patterns. Although a deletion within intron 2 of the DCDC2, encompassing the entire READ1 (hereafter READ1d), has been reported to be linked to structural and functional brain alterations, its impact on white matter connectivity was not fully explored. In this study, we investigated how the READ1d influences white matter network organization and its relationship with reading ability. Seventy-four children (47 M/27 F, age in months: 161 ± 22) with/without a diagnosis of DD and with/without READ1d underwent diffusion MRI, from which graph-theoretical analysis was performed. Statistical analyses tested the effects of READ1d, reading proficiency, and their interaction, with age, sex, IQ, and attention scores included as covariates. Regardless of reading performance, subjects with READ1d showed nominally significant lower global efficiency, local efficiency, and clustering coefficient compared to subjects without READ1d, with consistent effect directions across metrics; the nodal analysis revealed a significant effect of READ1d on a network spanning lateral, occipital and frontal cortex. Reading performance was associated with a network in the left occipital-temporal cortex at the level of nodal degree and a scattered bilateral network for local efficiency. These findings are consistent with an association between READ1d carrier status and subtle but widespread differences in network integration and nodal connectivity, observed regardless of reading performance, and offer a framework for future multimodal investigations into the genetic architecture of reading disorders.