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Use of Polygenic Risk Scores for Coronary Heart Disease in Ancestrally Diverse Populations

  • Cardiovascular Genomics (KG Aragam, Section Editor)
  • Published:
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Abstract

Purpose of review

A polygenic risk score (PRS) is a measure of genetic liability to a disease and is typically normally distributed in a population. Individuals in the upper tail of this distribution often have relative risk equivalent to that of monogenic form of the disease. The majority of currently available PRSs for coronary heart disease (CHD) have been generated from cohorts of European ancestry (EUR) and vary in their applicability to other ancestry groups. In this report, we review the performance of PRSs for CHD across different ancestries and efforts to reduce variability in performance including novel population and statistical genetics approaches.

Recent Findings

PRSs for CHD perform robustly in EUR populations but lag in performance in non-EUR groups, particularly individuals of African ancestry. Several large consortia have been established to enable genomic studies in diverse ancestry groups and develop methods to improve PRS performance in multi-ancestry contexts as well as admixed individuals. These include fine-mapping to ascertain causal variants, trans ancestry meta-analyses, and ancestry deconvolution in admixed individuals.

Summary

PRSs are being used in the clinical setting but enthusiasm has been tempered by the variable performance in non-EUR ancestry groups. Increasing diversity in genomic association studies and continued innovation in methodological approaches are needed to improve PRS performance in non-EUR individuals for equitable implementation of genomic medicine.

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Funding

I.J.K. was supported by NHGRI grant HG006379 and HG011710 as well as NHLBI grant K24 HL137010. D.J.S. was supported by the U.S. Public Health Service and NIH grant R35 GM140487. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. OD was supported by Mayo Clinic Clinician-Investigator Training Program.

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Authors and Affiliations

  1. Department of Internal Medicine, Mayo Clinic, Rochester, MN, 55905, USA

    Ozan Dikilitas

  2. Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Ozan Dikilitas & Iftikhar J. Kullo

  3. Mayo Clinician-Investigator Training Program, Mayo Clinic, Rochester, MN, 55905, USA

    Ozan Dikilitas

  4. Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, 55905, USA

    Daniel J. Schaid

  5. VA Palo Alto Health Care System, Palo Alto, CA, 94304, USA

    Catherine Tcheandjieu, Shoa L. Clarke & Themistocles L. Assimes

  6. Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Catherine Tcheandjieu, Shoa L. Clarke & Themistocles L. Assimes

  7. Gonda Vascular Center, Mayo Clinic, Rochester, MN, 55905, USA

    Iftikhar J. Kullo

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  1. Ozan Dikilitas
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Dikilitas, O., Schaid, D.J., Tcheandjieu, C. et al. Use of Polygenic Risk Scores for Coronary Heart Disease in Ancestrally Diverse Populations. Curr Cardiol Rep 24, 1169–1177 (2022). https://doi.org/10.1007/s11886-022-01734-0

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