Imaging genetics of language network functional connectivity reveals links with language-related abilities, dyslexia and handedness

Language is supported by a distributed network of brain regions with a particular contribution from the left hemisphere. A multi-level understanding of this network requires studying its genetic architecture. We used resting-state imaging data from 29,681 participants (UK Biobank) to measure connectivity between 18 left-hemisphere regions involved in multimodal sentence-level processing, as well as their right-hemisphere homotopes, and interhemispheric connections. Multivariate genome-wide association analysis of this total network, based on genetic variants with population frequencies > 1%, identified 14 genomic loci, of which three were also associated with asymmetry of intrahemispheric connectivity. Polygenic dispositions to lower language-related abilities, dyslexia and left-handedness were associated with generally reduced leftward asymmetry of functional connectivity. Exome-wide association analysis based on rare, protein-altering variants (frequencies[≤] 1%) suggested 7 additional genes. These findings shed new light on genetic contributions to language network organization and related behavioural traits.