• Genetics
• Coronary Artery Disease

Genome-wide association studies (GWASs) including hundreds of thousands of individuals have characterised the coronary artery disease (CAD) risk associated with millions of genetic variants that are common in the population.1 Polygenic risk scores (PRSs) for CAD summarise the risk of CAD conferred by these genetic variants into a single score. While each genetic variant only confers a modest increase in the risk of CAD, when taken together in the form of a PRS, they show a strong and robust association with incident CAD events that are largely independent of traditional risk factors and family history.2 One distinct advantage of PRSs is they can be measured early in life, prior to the accumulated effects of traditional risk factors and before there is evidence of family history for CAD, allowing for the possibility of early intervention in very high-risk individuals.

PRSs only appear to confer modest improvements in risk prediction beyond established non-genetic risk scores, with unclear clinical significance.2 3 Nevertheless, PRSs can identify a subset of the population with a high polygenic risk that is equivalent to the risk from familial hypercholesterolaemia mutations.4 Many countries implement cascade screening programmes for the identification of patients with familial hypercholesterolaemia, who then undergo early and intensive preventive interventions to lower their risk. In contrast, individuals with high polygenic risk are not identified and are not offered the same opportunities to become aware of and intervene on their risk.

While the clinical utility of PRSs thus remains to be firmly established, they have undoubtedly served as useful research tools, enabling the investigation of a range of research questions. Among these, one emerging area of research is the interplay between lifestyle …