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Predictive Utility of Polygenic Risk Scores for Coronary Heart Disease in Three Major Racial and Ethnic Groups

Ozan Dikilitas1, Daniel J Schaid2, Matthew L Kosel2

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

American Journal of Human Genetics
|May 11, 2020
PubMed

Insights

Polygenic risk scores (PRSs) for coronary heart disease (CHD) show potential clinical utility across diverse populations. However, their predictive power is reduced in African ancestry individuals, underscoring the need for diverse cohorts in PRS development.

Area of Science:

  • Genetics and Genomics
  • Cardiovascular Disease Epidemiology
  • Population Health

Background:

  • Polygenic risk scores (PRSs) for coronary heart disease (CHD) are primarily developed from European ancestry (EA) cohorts.
  • The predictive accuracy of these PRSs in non-European populations, such as African ancestry (AA) and Hispanic ethnicity (HE) individuals, remains uncertain.
  • This uncertainty limits the equitable clinical application of PRSs for CHD risk stratification.

Purpose of the Study:

  • To evaluate the association of PRSs with incident coronary heart disease (CHD) across diverse racial and ethnic groups within the U.S.
  • To compare the performance of restricted and genome-wide PRSs derived from EA cohorts in EA, AA, and HE individuals.
  • To identify the best performing PRS and assess its generalizability across ancestries.

Main Methods:

  • Utilized the eMERGE cohort comprising 45,645 EA, 7,597 AA, and 2,493 HE individuals.
  • Assessed two restricted PRSs (PRSTikkanen, PRSTada) and two genome-wide PRSs (PRSmetaGRS, PRSLDPred) developed from EA data.
  • Followed participants for a median of 11.1 years to ascertain 2,652 incident CHD events, analyzing hazard and odds ratios.

Main Results:

  • Genome-wide PRSs demonstrated stronger associations with CHD than restricted PRSs across all groups.
  • PRSmetaGRS showed significant association with CHD in EA, HE, and AA individuals (HRs per 1 SD increase: 1.53, 1.53, and 1.27, respectively).
  • Associations were comparable between EA and HE cohorts but significantly attenuated in AA individuals (pinteraction= 2.9 × 10-3).

Conclusions:

  • Genome-wide PRSs, particularly PRSmetaGRS, exhibit potential clinical utility for CHD risk prediction across diverse populations.
  • The predictive performance of PRSs derived from EA cohorts is significantly reduced in individuals of African ancestry.
  • There is a critical need to develop and validate PRSs using diverse ancestral and ethnic cohorts to ensure equitable risk prediction.

Keywords:
African Americancoronary artery diseasecoronary heart diseasegenome-wide polygenic scorehispanicischemic heart diseasemultiethnicpolygenic risk scoresrisk prediction

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