There is a dearth of large prospective studies to determine if genetic risk factors are useful predictors of health outcomes and if reporting them to individuals or physicians changes health behavior. The Coriell Personalized Medicine Collaborative® (CPMC, NJ, USA) is a prospective observational study with three cohorts - community, cancer and chronic disease cohorts. Participants provide detailed medical history through a dynamic internet-based portal. DNA is tested and personalized risk reports are provided for potentially actionable health conditions. To date, the community cohort has enrolled 4372 participants. The internet-based portal supplies educational content, captures phenotypic data and delivers customized risk reports. The Informed Cohort Oversight Board has approved 16 health conditions to date, and risk reports with genetic and nongenetic risks for six conditions have been released. The majority (87%) of participants who completed requisite questionnaires viewed at least one report. The CPMC is a cohort study delivering customized risk reports for actionable conditions using a web interface and measuring outcomes longitudinally.

Implementation of pharmacogenomics (PGx) in clinical care can lead to improved drug efficacy and reduced adverse drug reactions. However, there has been a lag in adoption of PGx tests in clinical practice. This is due in part to a paucity of rigorous systems for translating published clinical and scientific data into standardized diagnostic tests with clear therapeutic recommendations. Here we describe the Pharmacogenomics Appraisal, Evidence Scoring and Interpretation System (PhAESIS), developed as part of the Coriell Personalized Medicine Collaborative research study, and its application to seven commonly prescribed drugs.

Background: Familial hypercholesterolemia (FH) is the most common cardiovascular genetic disorder and, if left untreated, is associated with increased risk of premature atherosclerotic cardiovascular disease, the leading cause of preventable death in the United States. Although FH is common, fatal, and treatable, it is underdiagnosed and undertreated due to a lack of systematic methods to identify individuals with FH and limited uptake of cascade testing. Methods and Results: This mixed-method, multi-stage study will optimize, test, and implement innovative approaches for both FH identification and cascade testing in 3 aims. To improve identification of individuals with FH, in Aim 1, we will compare and refine automated phenotype-based and genomic approaches to identify individuals likely to have FH. To improve cascade testing uptake for at-risk individuals, in Aim 2, we will use a patient-centered design thinking process to optimize and develop novel, active family communication methods. Using a prospective, observational pragmatic trial, we will assess uptake and effectiveness of each family communication method on cascade testing. Guided by an implementation science framework, in Aim 3, we will develop a comprehensive guide to identify individuals with FH. Using the Conceptual Model for Implementation Research, we will evaluate implementation outcomes including feasibility, acceptability, and perceived sustainability as well as health outcomes related to the optimized methods and tools developed in Aims 1 and 2. Conclusions: Data generated from this study will address barriers and gaps in care related to underdiagnosis of FH by developing and optimizing tools to improve FH identification and cascade testing.