Polygenic Risk Scores: The Next Step for Improved Risk Stratification in Coronary Artery Disease?

Abstract

Despite significant advances in the management of coronary artery disease (CAD) and reductions in annual mortality rates in recent decades, this disease remains the leading cause of death worldwide. Consequently, there is an ongoing need for efforts to address this situation. Current clinical algorithms to identify at-risk patients are particularly inaccurate in moderate-risk individuals. For this reason, the need for ancillary tests has been suggested, including predictive genetic screening. As genetic studies rapidly expand and genomic data becomes more accessible, numerous genetic risk scores have been proposed to identify and evaluate an individual's susceptibility to developing diseases, including CAD. The field of genetics has indeed made substantial contributions to risk prediction, particularly in cases where children have parents with premature CAD, resulting in an increased risk of up to 75%. The polygenic risk scores (PRSs) have emerged as a potentially valuable tool for understanding and stratifying an individual's genetic risk. The PRS is calculated as a weighted sum of single-nucleotide variants present throughout the human genome, identifiable through genome-wide association studies, and associated with various cardiometabolic diseases. The use of PRSs holds promise, as it enables the development of personalized strategies for preventing or diagnosing specific pathologies early. Furthermore, it can complement existing clinical scores, increasing the accuracy of individual risk prediction. Consequently, the application of PRSs has the potential to impact the costs and adverse outcomes associated with CAD positively. This narrative review provides an overview of the role of PRSs in the context of CAD.

Figura Central. : Escores de Risco Poligênico: O Próximo Passo para Melhorar a Estratificação de Risco na Doença Arterial Coronariana?

Figura 1. – Aspectos essenciais de uma análise de escore de risco poligênico. AUC: área sob a curva ROC (receiver operator characteristic); GWAS: estudos de associação genômica ampla; LD: desequilíbrio de ligação; PRS: escore de risco poligênico; SNP: polimorfismos de nucleotídeo único.

Central Illustration. : Polygenic Risk Scores: The Next Step for Improved Risk Stratification in Coronary Artery Disease?

Figure 1. – Essential aspects of a polygenic risk score analysis. AUC: area under the receiver operating characteristic curve; GWAS: genome-wide association studies; LD: linkage disequilibrium; OR: odds ratio; PRS: polygenic risk score; SNPs: single nucleotide polymorphisms.