Implementing a Multi-Ancestry Polygenic Risk Score for Coronary Heart Disease in a Diverse Cohort.

Authors

Marwan Hamed, Mohammadreza Naderian, Hana Bangash, Valentina Hernandez, Gabriel Q Shaibi, Meliksah Arslan, Seyedmohammad Saadatagah, Alborz Sherafati, Alexandra Miller, Arailym Kamzabek, Oluwateniayo Ogunsan, Blake Goff, Brittney Davis, Cynthia Prows, James J Cimino, Josh Cortopassi, Leah Kottyan, Mark Beasley, Nita Limdi, Qiping Feng, Robb Rowley, Sharice Wood, Wei-Qi Wei, Yuan Luo, Teri A Manolio, Daniel Schaid, Pedro J Caraballo, Robert Freimuth, Richard R Sharp, Iftikhar J Kullo

Published in

Genetics in medicine : official journal of the American College of Medical Genetics. Pages 102662. Jul 11, 2026. Epub Jul 11, 2026.

Abstract

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_CHD: PGS004696) and assess outcomes after return of results (RoR).
PRS_CHD was considered alongside family history (FamHx_CHD), 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_CHD (top 5^th percentile) or FH received their results from study personnel, while participants with FamHx_CHD 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_CHD ≥95^th percentile and those with PRS_CHD 90^th-94^th percentile, using a regression discontinuity design. Secondary outcomes include ordering of screening tests, a new CHD diagnosis, and lifestyle changes.
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_CHD, high PRS_CHD 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.
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_CHD implementation in the context of FamHx_CHD, FH, and clinical risk, across the age spectrum in a diverse cohort.

PMID:
42434813
Bibliographic data and abstract were imported from PubMed on 11 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.