TY - JOUR
T1 - Predictive Utility of Polygenic Risk Scores for Coronary Heart Disease in Three Major Racial and Ethnic Groups
AU - Dikilitas, Ozan
AU - Schaid, Daniel J.
AU - Kosel, Matthew L.
AU - Carroll, Robert J.
AU - Chute, Christopher G.
AU - Denny, Joshua A.
AU - Fedotov, Alex
AU - Feng, Qi Ping
AU - Hakonarson, Hakon
AU - Jarvik, Gail P.
AU - Lee, Ming Ta Michael
AU - Pacheco, Jennifer A.
AU - Rowley, Robb
AU - Sleiman, Patrick M.
AU - Stein, C. Michael
AU - Sturm, Amy C.
AU - Wei, Wei Qi
AU - Wiesner, Georgia L.
AU - Williams, Marc S.
AU - Zhang, Yanfei
AU - Manolio, Teri A.
AU - Kullo, Iftikhar J.
N1 - Funding Information:
We are indebted to the investigators and participants of the electronic Medical Records and Genomics (eMERGE) Network. The eMERGE Network was initiated and funded by National Human Genome Research Institute (NHGRI) through the following grants: U01HG006828 (Cincinnati Children's Hospital Medical Center and Boston Children's Hospital); U01HG006830 (Children's Hospital of Philadelphia); U01HG006389 (Essentia Institute of Rural Health, Marshfield Clinic Research Foundation, and Pennsylvania State University); U01HG006382 (Geisinger Clinic); U01HG006375 (Group Health Cooperative and the University of Washington); U01HG006379 (Mayo Clinic); U01HG006380 (Icahn School of Medicine at Mount Sinai); U01HG006388 (Northwestern University); U01HG006378 (Vanderbilt University Medical Center); and U01HG006385 (Vanderbilt University Medical Center serving as the Coordinating Center). This phase of the eMERGE network was initiated and funded by the NHGRI through the following grants: U01HG8657 (Group Health Cooperative/University of Washington); U01HG8685 (Brigham and Women's Hospital); U01HG8672 (Vanderbilt University Medical Center); U01HG8666 (Cincinnati Children's Hospital Medical Center); U01HG6379 (Mayo Clinic); U01HG8679 (Geisinger Clinic); U01HG8680 (Columbia University Health Sciences); U01HG8684 (Children's Hospital of Philadelphia); U01HG8673 (Northwestern University); U01HG8701 (Vanderbilt University Medical Center serving as the Coordinating Center); U01HG8676 (Partners Healthcare and the Broad Institute); and U01HG8664 (Baylor College of Medicine). This work was also supported by the CTSA grant UL1 TR002377 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). I.J.K. was additionally supported by NIH grant K24 HL137010. 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.
Funding Information:
We are indebted to the investigators and participants of the electronic Medical Records and Genomics (eMERGE) Network. The eMERGE Network was initiated and funded by National Human Genome Research Institute (NHGRI) through the following grants: U01HG006828 ( Cincinnati Children's Hospital Medical Center and Boston Children's Hospital ); U01HG006830 ( Children's Hospital of Philadelphia ); U01HG006389 ( Essentia Institute of Rural Health , Marshfield Clinic Research Foundation , and Pennsylvania State University ); U01HG006382 ( Geisinger Clinic ); U01HG006375 ( Group Health Cooperative and the University of Washington ); U01HG006379 ( Mayo Clinic ); U01HG006380 ( Icahn School of Medicine at Mount Sinai ); U01HG006388 ( Northwestern University ); U01HG006378 ( Vanderbilt University Medical Center ); and U01HG006385 ( Vanderbilt University Medical Center serving as the Coordinating Center). This phase of the eMERGE network was initiated and funded by the NHGRI through the following grants: U01HG8657 ( Group Health Cooperative/University of Washington ); U01HG8685 ( Brigham and Women's Hospital ); U01HG8672 ( Vanderbilt University Medical Center ); U01HG8666 ( Cincinnati Children's Hospital Medical Center ); U01HG6379 ( Mayo Clinic ); U01HG8679 ( Geisinger Clinic ); U01HG8680 ( Columbia University Health Sciences ); U01HG8684 ( Children's Hospital of Philadelphia ); U01HG8673 ( Northwestern University ); U01HG8701 ( Vanderbilt University Medical Center serving as the Coordinating Center); U01HG8676 ( Partners Healthcare and the Broad Institute ); and U01HG8664 ( Baylor College of Medicine ). This work was also supported by the CTSA grant UL1 TR002377 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). I.J.K. was additionally supported by NIH grant K24 HL137010 . 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.
Publisher Copyright:
© 2020 American Society of Human Genetics
PY - 2020/5/7
Y1 - 2020/5/7
N2 - 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.
AB - 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.
KW - African American
KW - coronary artery disease
KW - coronary heart disease
KW - genome-wide polygenic score
KW - hispanic
KW - ischemic heart disease
KW - multiethnic
KW - polygenic risk scores
KW - risk prediction
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U2 - 10.1016/j.ajhg.2020.04.002
DO - 10.1016/j.ajhg.2020.04.002
M3 - Article
C2 - 32386537
AN - SCOPUS:85084159435
SN - 0002-9297
VL - 106
SP - 707
EP - 716
JO - American journal of human genetics
JF - American journal of human genetics
IS - 5
ER -