Four Decades of Inquiry Into the Genetic Bases of Specific Reading Disability.

Abstract

Purpose: This study investigated the genetic bases of specific reading disability (SRD) by systematically cataloging candidate genes reported as associated with SRD and reading-related processes over the last 4 decades and analyzing their evolutionary conservation, developmental expression patterns, and functional networks to address significant knowledge gaps in understanding the genetic architecture of reading (dis)ability.

Method: Through a comprehensive literature review, we identified 175 putative SRD (and reading-related processes) candidate genes (hereafter, SRD genes). Using bioinformatic approaches, we analyzed their evolutionary conservation across species, examined their expression patterns in developmental and single-cell transcriptome data sets from the Allen Brain Atlas, and performed functional pathway analyses to identify biological processes associated with these genes.

Results: SRD genes showed remarkable evolutionary conservation, with enrichment in ancient taxonomic groups. Developmental transcriptome analysis revealed two distinct gene clusters with expression differentiation around 24 postconception weeks: early genes associated with brain morphology development and later genes involved in synaptic signaling. Single-cell analysis identified cell-type-specific expression patterns and protein-protein interaction networks with hub genes potentially coordinating reading-related neural pathways.

Conclusions: Our findings challenge the notion of the existence of reading-specific genes, suggesting instead that SRD reflects the disruption of ancient evolutionary neural mechanisms operating within human-specific brain architecture. The identification of developmental expression transitions and functional networks provides insight into how genetic variation might impact reading development and offers potential targets for future clinical approaches to the identification and remediation of reading difficulties.

Supplemental material: https://doi.org/10.23641/asha.30290446.