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Open Access 01-12-2022 | Arterial Diseases | Research article

Polygenic risk score improves the accuracy of a clinical risk score for coronary artery disease

Authors: Austin King, Lang Wu, Hong-Wen Deng, Hui Shen, Chong Wu

Published in: BMC Medicine | Issue 1/2022

Abstract

Background

The value of polygenic risk scores (PRSs) towards improving guideline-recommended clinical risk models for coronary artery disease (CAD) prediction is controversial. Here we examine whether an integrated polygenic risk score improves the prediction of CAD beyond pooled cohort equations.

Methods

An observation study of 291,305 unrelated White British UK Biobank participants enrolled from 2006 to 2010 was conducted. A case–control sample of 9499 prevalent CAD cases and an equal number of randomly selected controls was used for tuning and integrating of the polygenic risk scores. A separate cohort of 272,307 individuals (with follow-up to 2020) was used to examine the risk prediction performance of pooled cohort equations, integrated polygenic risk score, and PRS-enhanced pooled cohort equation for incident CAD cases. The performance of each model was analyzed by discrimination and risk reclassification using a 7.5% threshold.

Results

In the cohort of 272,307 individuals (mean age, 56.7 years) used to analyze predictive accuracy, there were 7036 incident CAD cases over a 12-year follow-up period. Model discrimination was tested for integrated polygenic risk score, pooled cohort equation, and PRS-enhanced pooled cohort equation with reported C-statistics of 0.640 (95% CI, 0.634–0.646), 0.718 (95% CI, 0.713–0.723), and 0.753 (95% CI, 0.748–0.758), respectively. Risk reclassification for the addition of the integrated polygenic risk score to the pooled cohort equation at a 7.5% risk threshold resulted in a net reclassification improvement of 0.117 (95% CI, 0.102 to 0.129) for cases and − 0.023 (95% CI, − 0.025 to − 0.022) for noncases [overall: 0.093 (95% CI, 0.08 to 0.104)]. For incident CAD cases, this represented 14.2% correctly reclassified to the higher-risk category and 2.6% incorrectly reclassified to the lower-risk category.

Conclusions

Addition of the integrated polygenic risk score for CAD to the pooled cohort questions improves the predictive accuracy for incident CAD and clinical risk classification in the White British from the UK Biobank. These findings suggest that an integrated polygenic risk score may enhance CAD risk prediction and screening in the White British population.

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Title: Polygenic risk score improves the accuracy of a clinical risk score for coronary artery disease
Authors: Austin King
Lang Wu
Hong-Wen Deng
Hui Shen
Chong Wu
Publication date: 01-12-2022
Publisher: BioMed Central
Keyword: Arterial Diseases
Published in: BMC Medicine / Issue 1/2022
Electronic ISSN: 1741-7015
DOI: https://doi.org/10.1186/s12916-022-02583-y

At a glance: The STEP trials

Springer Medicine

Polygenic risk score improves the accuracy of a clinical risk score for coronary artery disease

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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