LAUSR

Background Specific Language Impairment (SLI) is a neurodevelopmental condition which causes linguistic deficits in children with otherwise normal development. SLI is demonstrably heritable (h2 ~ 0.6) and relatively common (occurring in ~7% of the population). Linkage, GWAS, and twin studies of SLI have produced mixed results with inconsistent replication, necessitating the integration of other forms of molecular data related to language ability into its study. The transcription factor FOXP2 is robustly associated with language ability, with perturbations to the coding region of the gene resulting in severe language deficits. However, such coding changes in FOXP2 are exceedingly rare. Variation in FOXP2's thousands of DNA binding sites is plentiful, on the other hand, making them attractive targets for interrogation in a common condition like SLI. Methods Genetic variants overlapping FOXP2 ChIP peak sites were extracted from the whole genome sequences of a cohort of 280 children (~140 SLI and ~140 control), and ranked based on association with overall language ability. Variation in the FOXP2 locus was also tested for association with language ability. Results Genes co-expressed with FOXP2 in the developing human brain and implicated in neurodevelopment were enriched for high-ranking FOXP2 binding sites. Despite these intriguing results, this variation – and that in the FOXP2 locus itself – was only able to explain a fraction of differences in total language ability. Discussion These results show the promise of integrating molecular data into genetic analysis of SLI, while demonstrating the inability of FOXP2 to fully explain the preponderance of variability in human language ability.