Implementing polygenic scores for heart disease

Tanya Brigden

14 June 2022


The recent Government report Genome UK: The Future of Healthcare underpins a series of strategies and policy papers that articulate the ambition to embed genomics into routine healthcare and to improve population health through disease prevention. 

Genetic contributions to disease risk are set at birth and remain stable throughout our lives making polygenic scores an attractive biomarker. There is considerable interest in their potential for earlier identification of individuals at increased risk of disease before conventional risk factors (such as high blood pressure or blood glucose levels) start to show. 

Gathering evidence

The PHG Foundation 2019 report, Polygenic scores, risk and cardiovascular disease examines the evidence around the readiness of polygenic scores as a clinical tool,  concluding that whilst a promising area, more evidence is needed to demonstrate clinical validity and utility. 

Efforts to gather this evidence are gaining pace, including what could be the largest ever health research programme Our Future Health, which aims to generate up to 5 million polygenic risk score assessments for volunteers  to see if and how they can be incorporated into smarter, more targeted clinical trials, research, and screening programmes. 

Other smaller studies are also being piloted, such as the HEART (Healthcare Evaluation of Absolute Risk Testing) study which is trialling an integrated risk tool (combining PGS with validated clinical risk factors) on 1000 participants who are eligible for an NHS Health Check. Depending on the results, studies such as these could provide the necessary evidence on whether and how polygenic scores can be best utilised at scale in the health service.

Turning to implementation

Given the speed of development and the considerable interest around the potential applications of polygenic scores, our recent report Implementing polygenic scores for cardiovascular disease into NHS Health Checks explores the changes needed to deliver polygenic score analysis within existing practice, using the NHS Health Check programme as an exemplar for early implementation. 

The NHS Health Check programme is a population risk assessment programme aimed at the early detection of chronic diseases in asymptomatic adults aged 40-75. The current programme uses a risk tool to generate a 10-year risk estimate based on a number of clinical risk factors (such as blood pressure, smoking status and age). 

Cardiovascular disease has a significant genetic component, suggesting it is a good candidate in which to trial the generation and inclusion of individual polygenic scores as an additional biomarker for risk. This possibility has been raised in the recent Review of the NHS Health Check programme and is being trialled in the HEART study. It is hoped that integrating polygenic scores into individual risk assessment will improve the predictive accuracy of the risk assessment. 

Better understanding of who falls into high and low risk groups should help target clinical intervention more effectively. However, given that the success of many primary prevention interventions rely on patients changing their behaviour (whether addressing lifestyle factors or compliance with treatments), further research is needed on how to support patients in achieving these goals.

What needs to change?

The NHS Health Checks process comprises a series of stages that could each be impacted by the integration of PGS

  • identification of eligible patients
  • the invitation to the patient and their decision to attend
  • gathering the necessary risk information at the Health Check appointment(s)
  • the communication of results back to the patient and consequent shared decision-making about risk management

We explore each of these aspects in Implementing polygenic scores for cardiovascular disease into NHS Health Checks, considering what would need to change if polygenic scores were incorporated. We found that only modest changes are needed when it comes to the interface between healthcare professionals and patients. 

It is not unusual for new risk factors to be incorporated into the risk tool and polygenic scores are arguably just another risk factor, and one that often does not need in-depth discussion with a patient. The routine clinical use of polygenic scores may even normalise the receipt of genomic information, to the extent that it becomes just one more piece of the risk puzzle. 

There is much debate about how to explain polygenic scores and concerns around the potential for confusion or misunderstanding, but in fact, there exists a firm foundation for this within primary care based on the long-established skill base for risk communication and shared decision-making. That being said, materials supporting informed choice would need to be updated to include the genetic component of the score (e.g. patient information leaflets, and patient-facing websites), and just-in-time resources would need to be developed for healthcare professionals delivering the assessments. 

One of the greatest challenges for a healthcare professional may arise where they see a patient who is at low risk based on conventional risk factors, but who has a very high polygenic score, or vice versa. Their polygenic score may even push them across a risk threshold and into another risk group. Guidance for clinicians on how to respond to different degrees of polygenic risk will be essential, as is clarity around appropriate enhanced or reduced interventions for borderline cases.

If clinical validity and utility can be demonstrated – and that is a big if - the implementation of polygenic score analysis into the NHS Health Check programme should be feasible. This is consistent with active consideration of improved stratified screening in other contexts. However, a host of issues will need careful planning for, including developing a robust testing infrastructure, creating professional guidance, delivering healthcare professional education and safeguarding patients’ expectations before polygenic scores can be implemented to bolster personalised prevention.

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