Approved Research

Characterizing the Incidence of ACMG Reportable Secondary Findings and Clinical Outcomes in a Large Prospective Cohort

Lay summary

Many rare cardiac diseases can be diagnosed through analysis of the patient's genome. Modern techniques analyze a patient's entire set of genes, or their genome. Although effective, these tests can result in incidental/secondary findings, where the test reveals genetic mutations unrelated to the original reason for testing. Mutations to some genes can result in potentially lethal diseases, and therefore the American College of Medical Genetics and Genomics created recommendations for diagnostic laboratories and clinicians to disclose these secondary findings to patients. These recommendations include several cardiac-related genes. Consequently, patients must be seen by medical specialists and be subject to medical testing and possibly interventions.  However, many individuals carry genetic mutations and the presence of a mutation does not always confer disease. This leaves many asymptomatic patients with unnecessary medical attention and increased anxiety. Furthermore, these patients may potentiate wait times for specialists and increase healthcare spending.

The aim of our research is to study the burden of secondary findings related to heart diseases from genomic testing on the population-level. We will use the public genetic mutation database ClinVar to identify genetic mutations associated with actionable genetic secondary findings. We will then quantify the incidence of secondary findings in the UK Biobank, a large prospective cohort containing genomic and clinical data from approximately 500 000 participants. Subsequently, we will analyze clinical data for the UK Biobank participants carrying these reportable genetic variants and classify participants with a positive or negative disease phenotype, allowing us to analyze the relationship between genotype and clinical outcomes within the context of the American College of Medical Genetics and Genomics reportable secondary findings list. We hypothesize that there will be a significant number of people within the UK biobank that have reportable cardiac genetic findings per current guidelines, however many will not have clinical findings related to a disease.

We anticipate this project to be completed 12 months after gaining access to the required data. This research will describe the scope of the genetic secondary findings issue and inform future system-level policies and interventions which will improve the quality of patient care and reduce expenditures. This research will also provide a foundation for future projects which may further describe the economic costs of secondary findings. Ultimately, we hope to decrease the number of patients who are unnecessarily being given medical attention due to their harmless genetic mutations.