General Information about the Genetic risk and Genomics application to Primary Prevention and Personalized medicine (G2P3)

In 2013, the American College of Medical Genetics (ACMG) recommended that clinical laboratories report back incidental findings for 56 (now 59) genes that cause severe disease and are clinically actionable. It is estimated that these genes affect 2-5% of the population (60,000-150,000 cases in the U.S.).

However, the utility of broader scale preventative testing for the presence of these genes has not been rigorously examined. Our central hypothesis is that genetic screening for germline variants in the ACMG 59 genes with a “prevention” panel in primary care clinics is efficacious and will produce a high return on investment (ROI).

An approximately 200 patient cohort from a primary care clinic will be tested with a 139-gene pre-curated medically actionable test (Invitae Laboratory). We will also determine if patients who meet clinical criteria to have these genes tested are being missed by traditional primary care intake or genetic counseling assessments. Key outcomes of cost saving and ROI, as well as longer-term effects on morbidity and mortality will be assessed.

Prevention using genomics, family history, and personal medical devices

By identifying clinical issues early, prior to clinical presentation, it will be possible to reduce expensive hospitalizations and complications of disease. The emerging approaches of clinical genomics only heightens the opportunity, but have not yet been tested extensively in a primary care setting.

We hypothesize that combining the monitoring of higher disease risk persons by exome sequencing and their use of personal medical devices will improve diagnostic yield, reduce extensive unnecessary ‘diagnostic odysseys’, reduce mortality, and reduce healthcare cost. We will test this hypothesis on ~200 patient cohort from a local concierge medicine practice. The participants will be enrolled in a longitudinal clinical research study using their retrospective medical history as a control.

Genotyping or exome sequencing and clinical family history of participants will identify individuals with elevated risk of cancer, diabetes, cardiological, and several other conditions. These risks will guide assignment and frequency of testing and monitoring with personal medical devices. Those with genetic and/or medical device data of concern will be referred to a specialist and followed up by monitoring with medical devices; treatment will be monitored as well. Outcomes of clinical statistics, changes in drug and treatment practices, patient quality of life, and a summary of total expenditures versus standard of care will be assessed.