Examining Procedural Learning and Corticostriatal Pathways for Individual Differences in Language: Testing Endophenotypes of DRD2/ANKK1.

The aim of the study was to explore whether genetic variation in the dopaminergic system is associated with procedural learning and the corticostriatal pathways in individuals with developmental language impairment (DLI). We viewed these two systems as endophenotypes and hypothesized that they would be more sensitive indicators of genetic effects than the language phenotype itself. Thus, we genotyped two SNPs in the DRD2/ANKK1 gene complex, and tested for their associations to the phenotype of DLI and the two endophenotypes. Results showed that individuals with DLI revealed poor procedural learning abilities and abnormal structures of the basal ganglia. Genetic variation in DRD2/ANKK1 was associated with procedural learning abilities and with microstructural differences of the caudate nucleus. The association of the language phenotype with these DRD2/ANKK1 polymorphisms was not significant, but the phenotype was significantly associated with the two endophenotypes. We suggest that procedural learning and the corticostriatal pathways could be used as effective endophenotypes to aid molecular genetic studies searching for genes predisposing to DLI.