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Polygenic Scores to Assess Atherosclerotic Cardiovascular Disease Risk: Clinical Perspectives and Basic Implications - PubMed

  • ️Wed Jan 01 2020

Review

Polygenic Scores to Assess Atherosclerotic Cardiovascular Disease Risk: Clinical Perspectives and Basic Implications

Krishna G Aragam et al. Circ Res. 2020.

Abstract

An individual's susceptibility to atherosclerotic cardiovascular disease is influenced by numerous clinical and lifestyle factors, motivating the multifaceted approaches currently endorsed for primary and secondary cardiovascular disease prevention. With growing knowledge of the genetic basis of atherosclerotic cardiovascular disease-in particular, coronary artery disease-and its contribution to disease pathogenesis, there is increased interest in understanding the potential clinical utility of a genetic predictor that might further refine the assessment and management of atherosclerotic cardiovascular disease risk. Rapid scientific and technological advances have enabled widespread genotyping efforts and dynamic research in the field of coronary artery disease genetic risk prediction. In this review, we describe how genomic analyses of coronary artery disease have been leveraged to create polygenic risk scores. We then discuss evaluations of the clinical utility of these scores, pertinent mechanistic insights gleaned, and practical considerations relevant to the implementation of polygenic risk scores in the health care setting.

Keywords: atherosclerosis; cardiovascular disease; coronary artery disease; genome-wide association study; genotype.

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Figures

Figure 1 –
Figure 1 –

Genome-wide association studies have identified 164 genetic risk loci associated with coronary artery disease, with many classified into distinct mechanistic pathways. From Erdmann et al. Cardiovascular Research 2018.

Figure 2 –
Figure 2 –

Development of polygenic risk scores. Modified from Choi et al. bioRxiv 2018.

Figure 3 –
Figure 3 –

Genome-wide polygenic risk scores: (A) identify a marked, inherited predisposition to CAD; (B) provide lifetime estimates of risk; and (C) add to the discriminative ability of clinical risk factors. Panel (A) from Khera et al. Nature Genetics 2018. Panels (B) and (C) from Inouye et al. JACC 2018.

Figure 4 –
Figure 4 –

Polygenic risk score as the “first risk factor” for coronary artery disease.

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