PROJECT SUMMARY (unchanged from currently approved project) In this project, we will develop and validate clinical polygenic risk scores (PRS) for six common diseases: coronary artery disease, atrial fibrillation, type 2 diabetes mellitus, breast cancer, colorectal cancer, and prostate cancer. This test will then be used in a point-of-care pragmatic randomized controlled trial of PRS testing and linked clinical recommendations compared to usual care (UC). Enrolled patients without a known diagnosis of any of the six target diseases will undergo clinical PRS genotyping. Patients with at least one PRS indicating high risk (odds ratio, ORPRS, ≥2.0) will be randomized to have them and their primary care provider receive their high-PRS results at baseline (PRS arm) or after a 24-month observation period (UC arm), reported along with evidence-based screening and management recommendations. Patients will be observed for 24 months for the primary clinical outcome of time-to-diagnosis of any one of the 6 target diseases. Secondary clinical outcomes will include changes in clinical management and patient health behaviors. Enrolled patients with all ORPRS<2.0 will be observed as concurrent controls for the same outcomes. Additional implementation outcomes will be collected over the course of the study, including provider knowledge and beliefs about PRS, patient activation, medication adherence, and costs.