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

Ozan Dikilitas, Daniel J. Schaid, Matthew L. Kosel, Robert J. Carroll, Christopher G. Chute, Joshua A. Denny, Alex Fedotov, Qi Ping Feng, Hakon Hakonarson, Gail P. Jarvik, Ming Ta Michael Lee, Jennifer A. Pacheco, Robb Rowley, Patrick M. Sleiman, C. Michael Stein, Amy C. Sturm, Wei Qi Wei, Georgia L. Wiesner, Marc S. Williams, Yanfei ZhangTeri A. Manolio, Iftikhar J. Kullo

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Because polygenic risk scores (PRSs) for coronary heart disease (CHD) are derived from mainly European ancestry (EA) cohorts, their validity in African ancestry (AA) and Hispanic ethnicity (HE) individuals is unclear. We investigated associations of “restricted” and genome-wide PRSs with CHD in three major racial and ethnic groups in the U.S. The eMERGE cohort (mean age 48 ± 14 years, 58% female) included 45,645 EA, 7,597 AA, and 2,493 HE individuals. We assessed two restricted PRSs (PRSTikkanen and PRSTada; 28 and 50 variants, respectively) and two genome-wide PRSs (PRSmetaGRS and PRSLDPred; 1.7 M and 6.6 M variants, respectively) derived from EA cohorts. Over a median follow-up of 11.1 years, 2,652 incident CHD events occurred. Hazard and odds ratios for the association of PRSs with CHD were similar in EA and HE cohorts but lower in AA cohorts. Genome-wide PRSs were more strongly associated with CHD than restricted PRSs were. PRSmetaGRS, the best performing PRS, was associated with CHD in all three cohorts; hazard ratios (95% CI) per 1 SD increase were 1.53 (1.46–1.60), 1.53 (1.23–1.90), and 1.27 (1.13–1.43) for incident CHD in EA, HE, and AA individuals, respectively. The hazard ratios were comparable in the EA and HE cohorts (pinteraction = 0.77) but were significantly attenuated in AA individuals (pinteraction = 2.9 × 10−3). These results highlight the potential clinical utility of PRSs for CHD as well as the need to assemble diverse cohorts to generate ancestry- and ethnicity PRSs.

Original languageEnglish (US)
Pages (from-to)707-716
Number of pages10
JournalAmerican journal of human genetics
Volume106
Issue number5
DOIs
StatePublished - May 7 2020

Keywords

  • African American
  • coronary artery disease
  • coronary heart disease
  • genome-wide polygenic score
  • hispanic
  • ischemic heart disease
  • multiethnic
  • polygenic risk scores
  • risk prediction

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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  • Cite this

    Dikilitas, O., Schaid, D. J., Kosel, M. L., Carroll, R. J., Chute, C. G., Denny, J. A., Fedotov, A., Feng, Q. P., Hakonarson, H., Jarvik, G. P., Lee, M. T. M., Pacheco, J. A., Rowley, R., Sleiman, P. M., Stein, C. M., Sturm, A. C., Wei, W. Q., Wiesner, G. L., Williams, M. S., ... Kullo, I. J. (2020). Predictive Utility of Polygenic Risk Scores for Coronary Heart Disease in Three Major Racial and Ethnic Groups. American journal of human genetics, 106(5), 707-716. https://doi.org/10.1016/j.ajhg.2020.04.002