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As the burden of cardiovascular disease increases in the United States, the importance of enhanced screening tools, early risk prediction, and prevention strategies grows. Novel risk scoring methods, including polygenic risk scores (PRS), may help identify patients that benefit from early intervention and risk modification. In this episode, we discuss how a PRS is calculated, how to incorporate a PRS into clinical practice, and current barriers to the equitable implementation of risk scores. In terms of frontiers in clinical genetics we also discuss the burgeoning field of pharmacogenetics and how pharmacogenetics may be used to identify responders and non-responders to certain therapies.\n\n\n\nJoin CardioNerds Dr. Jessie Holtzman (CardioNerds Academy Chief and Chief Resident and soon FIT at UCSF), Dr. Alaa Diab (CardioNerds Academy Fellow and Medicine Resident at GBMC), and student doctor Hirsh Elhence (CardioNerds Academy Intern and medical student at USC Keck School of Medicine) as they discuss frontiers in clinical genetics with Dr. Pradeep Natarajan (Director of Preventive Cardiology, Massachusetts General Hospital). Audio editing by\xa0CardioNerds Academy Intern, student doctor\xa0Akiva Rosenzveig.\n\n\n\nThis episode was developed in collaboration with the American Society of Preventive Cardiology and is supported with unrestricted educational funds from Illumina, Inc. All CardioNerds content is planned, produced, and reviewed solely by CardioNerds.\n\n\n\nThis CardioNerds Cardiovascular Genomics series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs.\n\n\n\n\n\nPearls \u2022 Notes \u2022 References \n\n\n\n\n\n\n\n\n\n\n\nCardioNerds Cardiovascular Genomics PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll\n\n\n\n\n\nCardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron!\n\n\n\n\n\n\n\n\n\nPearls - Frontiers in Clinical Genetics in Cardiovascular Prevention \n\n\n\n\nFor common diseases like coronary artery disease, rare mutations may confer a several-fold increased risk of disease \u2013 for instance, in familial hypercholesterolemia, a single rare mutation may confer as much as a three-fold increase in risk of coronary artery disease. However, for most common diseases, the overall cumulative impact of several common genetic variants may be greater than that of a monogenetic trait.\n\n\n\nFamily history is a particularly coarse predictor of CV risk, highlighting the need for polygenic risk scores. In particular, younger patients with borderline cardiovascular risk may benefit from the use of a polygenic risk score in the determination of their overall cardiovascular risk profile.\n\n\n\nA polygenic risk score (PRS) is a weighted sum of several risk-conferring alleles. The weight assigned to an allele is determined by the strength of the association between the allele and CV disease, as determined by genome-wide association studies (GWAS).\n\n\n\nThe data used for genome-wide associated studies in cardiovascular disease have historically included populations primarily of European ancestry. However, more data is being collected from diverse patient cohorts to increase the external validity and broader applicability of such studies.\n\n\n\nPharmacogenetic polygenic risk scores may be used to predict drug efficacy and toxicity, as well as to identify biologically plausible drug targets for clinical trial design.\n\n\n\n\nShow notes - Frontiers in Clinical Genetics in Cardiovascular Prevention \n\n\n\nWhat is a polygenic risk score (PRS)?\n\n\n\n\nMonogenic conditions are those in which a variant in a single gene causes a pathological phenotype. For example, familial hypercholesterolemia is often the result of a mutated allele in the LDL receptor gene.\n\n\n\nIn contrast, polygenic risk suggests that there are variants in multiple genes that all confer risk independently, each with a small individual effect size. By aggregating many variants,