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验证一种综合风险工具,包括多基因风险评分,用于多种族裔和血统的动脉粥样硬化性心血管疾病。

Validation of an Integrated Risk Tool, Including Polygenic Risk Score, for Atherosclerotic Cardiovascular Disease in Multiple Ethnicities and Ancestries.

机构信息

Genomics plc, Oxford, UK.

Genomics plc, Oxford, UK.

出版信息

Am J Cardiol. 2021 Jun 1;148:157-164. doi: 10.1016/j.amjcard.2021.02.032. Epub 2021 Mar 3.


DOI:10.1016/j.amjcard.2021.02.032
PMID:33675770
Abstract

The American College of Cardiology / American Heart Association pooled cohort equations tool (ASCVD-PCE) is currently recommended to assess 10-year risk for atherosclerotic cardiovascular disease (ASCVD). ASCVD-PCE does not currently include genetic risk factors. Polygenic risk scores (PRSs) have been shown to offer a powerful new approach to measuring genetic risk for common diseases, including ASCVD, and to enhance risk prediction when combined with ASCVD-PCE. Most work to date, including the assessment of tools, has focused on performance in individuals of European ancestries. Here we present evidence for the clinical validation of a new integrated risk tool (IRT), ASCVD-IRT, which combines ASCVD-PCE with PRS to predict 10-year risk of ASCVD across diverse ethnicity and ancestry groups. We demonstrate improved predictive performance of ASCVD-IRT over ASCVD-PCE, not only in individuals of self-reported White ethnicities (net reclassification improvement [NRI]; with 95% confidence interval = 2.7% [1.1 to 4.2]) but also Black / African American / Black Caribbean / Black African (NRI = 2.5% [0.6-4.3]) and South Asian (Indian, Bangladeshi or Pakistani) ethnicities (NRI = 8.7% [3.1 to 14.4]). NRI confidence intervals were wider and included zero for ethnicities with smaller sample sizes, including Hispanic (NRI = 7.5% [-1.4 to 16.5]), but PRS effect sizes in these ethnicities were significant and of comparable size to those seen in individuals of White ethnicities. Comparable results were obtained when individuals were analyzed by genetically inferred ancestry. Together, these results validate the performance of ASCVD-IRT in multiple ethnicities and ancestries, and favor their generalization to all ethnicities and ancestries.

摘要

美国心脏病学会/美国心脏协会的队列方程工具(ASCVD-PCE)目前被推荐用于评估动脉粥样硬化性心血管疾病(ASCVD)的 10 年风险。ASCVD-PCE 目前不包括遗传风险因素。多基因风险评分(PRS)已被证明是一种评估常见疾病遗传风险的强大新方法,包括 ASCVD,并与 ASCVD-PCE 相结合可增强风险预测。迄今为止,大多数工作,包括工具评估,都集中在欧洲血统个体的表现上。在这里,我们提供了一种新的综合风险工具(IRT)ASCVD-IRT 的临床验证证据,该工具将 ASCVD-PCE 与 PRS 相结合,可预测不同种族和祖先群体的 10 年 ASCVD 风险。我们证明了 ASCVD-IRT 优于 ASCVD-PCE 的预测性能,不仅在自我报告为白人种族的个体中(净重新分类改善[NRI];置信区间为 2.7%[1.1-4.2]),而且在黑种人/非裔美国人/黑加勒比/非裔黑人(NRI=2.5%[0.6-4.3])和南亚(印度、孟加拉或巴基斯坦)族裔中(NRI=8.7%[3.1-14.4])。对于样本量较小的族裔,NRI 的置信区间较宽且包含零,包括西班牙裔(NRI=7.5%[-1.4-16.5]),但这些族裔的 PRS 效应大小是显著的,与白人个体中观察到的大小相当。当按遗传推断的祖源对个体进行分析时,也得到了类似的结果。综上所述,这些结果验证了 ASCVD-IRT 在多种族裔和祖源中的性能,并支持将其推广到所有族裔和祖源。

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[1]
Impact of genetic risk and lifestyles on cardiovascular disease-free and total life expectancy: a cohort study.

Genome Med. 2025-7-22

[2]
Clinical Algorithms and the Legacy of Race-Based Correction: Historical Errors, Contemporary Revisions and Equity-Oriented Methodologies for Epidemiologists.

Clin Epidemiol. 2025-7-12

[3]
Performance of deep-learning-based approaches to improve polygenic scores.

Nat Commun. 2025-6-2

[4]
Methodological opportunities in genomic data analysis to advance health equity.

Nat Rev Genet. 2025-5-15

[5]
Clinical utility and implementation of polygenic risk scores for predicting cardiovascular disease: A clinical consensus statement of the ESC Council on Cardiovascular Genomics, the ESC Cardiovascular Risk Collaboration, and the European Association of Preventive Cardiology.

Eur Heart J. 2025-4-15

[6]
2025 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.

Circulation. 2025-2-25

[7]
Genetic proxies for clinical traits are associated with increased risk of severe COVID-19.

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[8]
Development and Evaluation of a Comprehensive Prediction Model for Incident Coronary Heart Disease Using Genetic, Social, and Lifestyle-Psychological Factors: A Prospective Analysis of the UK Biobank.

Ann Intern Med. 2025-1

[9]
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Circulation. 2024-11-19

[10]
An 8-SNP LDL Cholesterol Polygenic Score: Associations with Cardiovascular Risk Traits, Familial Hypercholesterolemia Phenotype, and Premature Coronary Heart Disease in Central Romania.

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