PROJECT SUMMARY / ABSTRACT - PROJECT 1 The field of pharmacogenomics has progressed from the discovery of genetic variants that cause variable function of drug metabolism enzymes to a cornerstone of clinical precision medicine. However, there are limited data supporting drug-gene associations for children and for women during and after pregnancy. The unique physiology of childhood and pregnancy demand validation of pharmacogenomic signals prior to clinical implementation. These knowledge gaps are compounded for individuals from minority populations, who have been underrepresented and thus underserved by genomic research and specifically pharmacogenomic studies. The primary objective of this project is to advance research and support clinical implementation in pharmacogenomics for children and pregnant women. Our work will use a community engaged approach to: 1) illuminate knowledge of, attitudes about, and priorities for pharmacogenomics; 2) validate pharmacogenomic associations for pediatric and maternal populations using the innovative and generalizable strategy of electronic health records phenotyping; 3) identify and quantify variants with unknown functional consequence in diverse individuals in order to inform future research efforts and reduce disparities. Aim 1 will assess the knowledge and attitudes regarding pharmacogenomic testing among diverse cohorts of children with chronic disease and pregnant women, before and after receiving pharmacogenomic test results. This aim will begin with a Community Engagement Studio to identify strategies to facilitate and enhance inclusion of children with chronic health conditions, pregnant women, minorities, and those with disabilities in pharmacogenomic research. We will then perform surveys before and after pharmacogenomic testing and return of results. Aim 2 will leverage our large biobank resource to validate high-frequency drug-gene interactions in women and children to enable evidence-based clinical implementation for these populations and identify novel signals for further study. This aim will generate electronic health records phenotyping methods and tools to efficiently complete the aim and facilitate future research at our site and others. Aim 3 will identify and quantify genetic variants of unknown function in pharmacogenomic genes among children and pregnant women in a diverse cohort of biobank participants, informing the spectrum of genomic diversity requiring characterization. Overall, accomplishing these aims will address critical knowledge deficits for precision therapeutics for pediatric and maternal populations.