Genet Med. 2026 Jul 11:102662. doi: 10.1016/j.gim.2026.102662. Online ahead of print.
ABSTRACT
PURPOSE: We describe a prospective cohort study (NCT05277116) conducted in phase IV of the electronic MEdical Records and GEnomics (eMERGE) Network to implement a multi-ancestry polygenic risk score for coronary heart disease (PRS: PGS004696) and assess outcomes after return of results (RoR).
METHODS: PRS was considered alongside family history (FamHx), monogenic risk from familial hypercholesterolemia (FH), and clinical risk factors, to return CHD risk as part of a Genome Informed Risk Assessment (GIRA) report. Participants with high PRS (top 5th percentile) or FH received their results from study personnel, while participants with FamHx were informed by mail/email. Results were placed in the electronic health record and communicated to the primary care provider. The primary outcome of initiation/intensification of lipid lowering therapy within 12 months after RoR is compared between participants with PRS ≥95th percentile and those with PRS 90th-94th percentile, using a regression discontinuity design. Secondary outcomes include ordering of screening tests, a new CHD diagnosis, and lifestyle changes.
RESULTS: By April 2025, 20,421 adults were enrolled: mean age 50±15 years (range 18-75 years), 68% female, 50% belonging to health disparity groups, and 40% non-White by self-report. Prevalence of CHD, FamHx, high PRS and FH was 4.0%, 10.2%, 4.3% and 0.7%, respectively; 14.3% had at least one of the three CHD genetic risk factors and CHD risk estimates were highest in those who self-reported as Black.
CONCLUSION: The prevalence of increased genetic risk for CHD was high and at least one of the three genetic risk factors for CHD was present in 14.2% of the cohort. Analyses are underway to assess outcomes after PRS implementation in the context of FamHx, FH, and clinical risk, across the age spectrum in a diverse cohort.
PMID:42434813 | DOI:10.1016/j.gim.2026.102662