Structural connectivity associations with dyslexia-linked genes identifies the left insula as the key phonological hub

Dyslexia is characterized by difficulties acquiring fluent reading skills, it is heritable, possibly involving neural disconnection. Results from well-powered genome-wide association studies can be harnessed to uncover associations between dyslexia genetic liability with the macroscale white matter connectome to pinpoint neurobiology. Using multimodal magnetic resonance imaging data from 40,372 adults (44-85 years) in the UK Biobank, we examined associations between dyslexia polygenic indices (PGI) and regional grey matter structure and hub-based white matter connectivity across 85 regions (68 cortical; 17 subcortical). The left insula showed negative PGI associations across grey and white matter measures, with replication in 1,068 adults (26-84 years) from the Generation Scotland: Scottish Family Health Study. Connectivity of the left insula mediated the association between dyslexia PGI and phonological short-term memory/reading skill in both cohorts. Polygenic dyslexia predisposition is thus reflected in both structural and connectomic properties of the left insula and consistent with phonological deficit theory.