TY - JOUR
T1 - Polygenic risk score in comparison with C-reactive protein for predicting incident coronary heart disease
AU - Aday, Aaron W.
AU - Bagheri, Minoo
AU - Vaitinadin, Nataraja Sarma
AU - Mosley, Jonathan D.
AU - Wang, Thomas J.
N1 - Publisher Copyright:
© 2023 Elsevier B.V.
PY - 2023/8
Y1 - 2023/8
N2 - Background and aims: Despite interest in the use of polygenic risk scores (PRS) for predicting coronary heart disease (CHD) risk, the clinical utility of PRS compared to conventional risk factors has not been demonstrated. We compared the performance of PRS with that of high-sensitivity C-reactive protein (hsCRP) in two well-established cohorts. Methods: The study population included individuals of European ancestry free of baseline CHD from ARIC (N = 13,113) and the Framingham Offspring Study (FHS) (N = 2,696). The primary predictors included a validated PRS consisting of >6.6 million single nucleotide polymorphisms and hsCRP. The outcome was incident CHD, defined as non-fatal or fatal myocardial infarction. We compared the performance of both predictors after adjusting for the Pooled Cohort Equations in multivariable-adjusted Cox regression models. We assessed discrimination and reclassification using c-statistics and net reclassification improvement. Results: Incident CHD occurred in 565 ARIC and 153 FHS participants. In multivariable-adjusted models, both PRS and hsCRP were associated with incident CHD (p < 0.05 in both cohorts). In models incorporating both predictors, strengths of association were similar. For instance, in ARIC, the hazard ratio per SD increment was 1.38 (95% CI, 1.27–1.50, p = 2.94 × 10−14) for PRS and 1.41 (1.30–1.55, p = 3.10 × 10−15) for hsCRP. Neither predictor significantly increased model discrimination or net reclassification when compared with models containing the Pooled Cohort Equations alone. Conclusions: In two independent cohorts, PRS performed similarly to hsCRP for the prediction of CHD risk. These findings suggest PRS does not have unique clinical utility beyond this widely-available, inexpensive measure of risk in unselected middle-aged populations.
AB - Background and aims: Despite interest in the use of polygenic risk scores (PRS) for predicting coronary heart disease (CHD) risk, the clinical utility of PRS compared to conventional risk factors has not been demonstrated. We compared the performance of PRS with that of high-sensitivity C-reactive protein (hsCRP) in two well-established cohorts. Methods: The study population included individuals of European ancestry free of baseline CHD from ARIC (N = 13,113) and the Framingham Offspring Study (FHS) (N = 2,696). The primary predictors included a validated PRS consisting of >6.6 million single nucleotide polymorphisms and hsCRP. The outcome was incident CHD, defined as non-fatal or fatal myocardial infarction. We compared the performance of both predictors after adjusting for the Pooled Cohort Equations in multivariable-adjusted Cox regression models. We assessed discrimination and reclassification using c-statistics and net reclassification improvement. Results: Incident CHD occurred in 565 ARIC and 153 FHS participants. In multivariable-adjusted models, both PRS and hsCRP were associated with incident CHD (p < 0.05 in both cohorts). In models incorporating both predictors, strengths of association were similar. For instance, in ARIC, the hazard ratio per SD increment was 1.38 (95% CI, 1.27–1.50, p = 2.94 × 10−14) for PRS and 1.41 (1.30–1.55, p = 3.10 × 10−15) for hsCRP. Neither predictor significantly increased model discrimination or net reclassification when compared with models containing the Pooled Cohort Equations alone. Conclusions: In two independent cohorts, PRS performed similarly to hsCRP for the prediction of CHD risk. These findings suggest PRS does not have unique clinical utility beyond this widely-available, inexpensive measure of risk in unselected middle-aged populations.
KW - C-reactive protein
KW - Coronary heart disease
KW - Polygenic risk scores
KW - Risk prediction
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U2 - 10.1016/j.atherosclerosis.2023.117194
DO - 10.1016/j.atherosclerosis.2023.117194
M3 - Article
C2 - 37536150
AN - SCOPUS:85166616959
SN - 0021-9150
VL - 379
JO - Atherosclerosis
JF - Atherosclerosis
M1 - 117194
ER -