Dataset Information

Polygenic risk score in comparison with C-reactive protein for predicting incident coronary heart disease.

ABSTRACT:

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.

SUBMITTER: Aday AW

PROVIDER: S-EPMC10529589 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

Polygenic risk score in comparison with C-reactive protein for predicting incident coronary heart disease.

Aday Aaron W AW Bagheri Minoo M Vaitinadin Nataraja Sarma NS Mosley Jonathan D JD Wang Thomas J TJ

Atherosclerosis 20230726

<h4>Background and aims</h4>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.<h4>Methods</h4>The study population included individuals of European ancestry free of baseline CHD from ARIC (N = 13,113) and the Framingham Offs ...[more]

PMID: 37536150

Similar Datasets

Project description:ImportancePolygenic risk scores comprising millions of single-nucleotide polymorphisms (SNPs) could be useful for population-wide coronary heart disease (CHD) screening.ObjectiveTo determine whether a polygenic risk score improves prediction of CHD compared with a guideline-recommended clinical risk equation.Design, setting, and participantsA retrospective cohort study of the predictive accuracy of a previously validated polygenic risk score was assessed among 4847 adults of white European ancestry, aged 45 through 79 years, participating in the Atherosclerosis Risk in Communities (ARIC) study and 2390 participating in the Multi-Ethnic Study of Atherosclerosis (MESA) from 1996 through December 31, 2015, the final day of follow-up. The performance of the polygenic risk score was compared with that of the 2013 American College of Cardiology and American Heart Association pooled cohort equations.ExposuresGenetic risk was computed for each participant by summing the product of the weights and allele dosage across 6 630 149 SNPs. Weights were based on an international genome-wide association study.Main outcomes and measuresPrediction of 10-year first CHD events (including myocardial infarctions, fatal coronary events, silent infarctions, revascularization procedures, or resuscitated cardiac arrest) assessed using measures of model discrimination, calibration, and net reclassification improvement (NRI).ResultsThe study population included 4847 adults from the ARIC study (mean [SD] age, 62.9 [5.6] years; 56.4% women) and 2390 adults from the MESA cohort (mean [SD] age, 61.8 [9.6] years; 52.2% women). Incident CHD events occurred in 696 participants (14.4%) and 227 participants (9.5%), respectively, over median follow-up of 15.5 years (interquartile range [IQR], 6.3 years) and 14.2 (IQR, 2.5 years) years. The polygenic risk score was significantly associated with 10-year CHD incidence in ARIC with hazard ratios per SD increment of 1.24 (95% CI, 1.15 to 1.34) and in MESA, 1.38 (95% CI, 1.21 to 1.58). Addition of the polygenic risk score to the pooled cohort equations did not significantly increase the C statistic in either cohort (ARIC, change in C statistic, -0.001; 95% CI, -0.009 to 0.006; MESA, 0.021; 95% CI, -0.0004 to 0.043). At the 10-year risk threshold of 7.5%, the addition of the polygenic risk score to the pooled cohort equations did not provide significant improvement in reclassification in either ARIC (NRI, 0.018, 95% CI, -0.012 to 0.036) or MESA (NRI, 0.001, 95% CI, -0.038 to 0.076). The polygenic risk score did not significantly improve calibration in either cohort.Conclusions and relevanceIn this analysis of 2 cohorts of US adults, the polygenic risk score was associated with incident coronary heart disease events but did not significantly improve discrimination, calibration, or risk reclassification compared with conventional predictors. These findings suggest that a polygenic risk score may not enhance risk prediction in a general, white middle-aged population.

Dataset Information

Polygenic risk score in comparison with C-reactive protein for predicting incident coronary heart disease.

Background and aims

Methods

Results

Conclusions

Publications

Polygenic risk score in comparison with C-reactive protein for predicting incident coronary heart disease.

Similar Datasets

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