PROJECT SUMMARY. Specific Language impairment (SLI) is a common, life-long communication disorder characterized by difficulties acquiring grammar and vocabulary that affect children's quality of life, success in school, and livelihood. There is an urgent need to increase identification and treatment of children with SLI. Although SLI is known to be heritable, the underlying neurobiology of the disorder is not yet clear. Recent work by the PI has shown robust associations between rhythm and grammar traits in children, pointing to rhythm resilience as a variable involved in spoken grammar skills. Emerging evidence in the field points to co-morbid rhythm deficits and grammatical deficits in SLI, pointing to weaknesses in rhythm sensitivity as an SLI risk factor. Furthermore, rhythm and grammatical traits are both heritable, and both involve dynamically orienting attention to hierarchical structure over time, but no prior study has directly compared the genetic basis of rhythm and grammar. Here we take an understudied but promising approach to investigating potentially shared genetic architecture to rhythm deficits and SLI. Since sound patterns (across species) used to communicate are organized rhythmically, it is highly likely that present-day speech and language capacities are built on pre- existing genetic architecture for communication, which may include the rhythmic aspect of communication. Children with SLI may thus have heritable rhythm deficits that impair their ability (via common neurobiology) to process the structure of language during grammatical acquisition. The present proposal integrates new methods of genome analysis with rhythm cognition experiments aimed at understanding the mechanisms underlying the potential contribution of rhythm deficits to SLI. Aim 1 harnesses large-sample bio-repositories and extant data with Genome-Wide Association Studies (GWAS) methodology to characterize the genetic architecture of developmental language disorder. This approach allows us to construct the largest sample sizes yet for developing a genetic prediction model for SLI and to investigate the clinical significance of genes involved in SLI. Aim 2 utilizes a GWAS approach in a novel dataset to provide important new knowledge on the genetic basis of rhythm. Armed with novel knowledge about the neurobiological markers of SLI and rhythm deficits, we will then investigate a potential influence of rhythm on grammar-related traits (Aim 3a) and grammar states (Aim 3b), using an innovative selection of genomic analyses and a series of targeted laboratory experiments in children with SLI. By testing this framework of rhythm risk and resilience, these studies lay essential groundwork for multiple future avenues of improving identification and treatment of children with SLI. This project directly responds to NIDCD's call to identify genetic factors and co-occurring conditions that contribute to language impairment and to develop biomarkers of SLI. Moreover, new...