Project Summary Speech-language impairments have been clinically and genetically linked with risks for mental health disorders, poor physical health, and poor educational outcomes. However, large-scale studies of speech-language deficits primarily remain the purview of research on learning disabilities and developmental disorders (e.g., articulation and fluency disorders; developmental language disorder; autism), underestimating the health impact of speech and language traits for all individuals. This project aims to investigate the overall health impact of speech and language difficulties, disorders, and risk. Specifically, we use unbiased, data-driven, computational approaches to examine the medical "phenome", or entire collection of health and disease outcomes (phenotypes) found in the All of Us Electronic Health Records (EH Rs). These phenome-wide association studies (PheWAS) have great potential to discover comorbidities, shared genetic risk for multiple health conditions, and identify targets for early intervention and therapies. In Aim 1 studies, we characterize associations between speech-language difficulties or disorders, and the entirety of the medical phenome. In Aim 2A and 28 studies, we investigate how genetic predispositions for speech-language abilities that have not been measured in All of Us participants (e.g., spelling; phonemic awareness), are associated with the entire medical phenome. In Aim 2A, we focus on genetic risk markers that are derived directly from common genetic variants associated with speech-language phenotypes; and in Aim 28 we build on this by additionally incorporating aspects of the transcriptome (e.g., gene expression), which improves portability of genetic risk predictions across multiple ancestry, and particularly in African Americans - a community who are highly underrepresented in biomedical research, and both historically and presently subject to systemic health inequity. Our approach, which is agnostic to specific clinical phenotypes, symptoms, diagnoses, or disorders, will reveal population-level health and disease outcomes associated with speech-language traits in populations that are usually underrepresented in biomedical research. This project directly responds to the call to make discoveries using high-quality All of Us data; advances the NIDCD mission to improve the lives of people with communication disorders; and enhances diversity in genomics research through the use of diverse data, and through opportunities for diversifying the workforce. By combining precision medicine techniques with a health equity and community-engaged focus, findings from this project will address critical health needs for subsets of individuals with certain clinical and/or genetic risk factors related to speech and language, as well as entire communities in whom communication traits/disorders have been understudied.