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

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 C...

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Published in:	American journal of human genetics Vol. 106; no. 5; p. 707
Main Authors:	Dikilitas, Ozan, Schaid, Daniel J, Kosel, Matthew L, Carroll, Robert J, Chute, Christopher G, Denny, Joshua A, Fedotov, Alex, Feng, QiPing, Hakonarson, Hakon, Jarvik, Gail P, Lee, Ming Ta Michael, Pacheco, Jennifer A, Rowley, Robb, Sleiman, Patrick M, Stein, C Michael, Sturm, Amy C, Wei, Wei-Qi, Wiesner, Georgia L, Williams, Marc S, Zhang, Yanfei, Manolio, Teri A, Kullo, Iftikhar J
Format:	Journal Article
Language:	English
Published:	United States 07.05.2020
Subjects:	coronary artery disease risk prediction hispanic ischemic heart disease coronary heart disease multiethnic genome-wide polygenic score African American polygenic risk scores
ISSN:	1537-6605, 1537-6605
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Summary:	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 (PRS and PRS ; 28 and 50 variants, respectively) and two genome-wide PRSs (PRS and PRS ; 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. PRS , 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 (p = 0.77) but were significantly attenuated in AA individuals (p = 2.9 × 10 ). 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.
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ISSN:	1537-6605 1537-6605
DOI:	10.1016/j.ajhg.2020.04.002