The Promise and Pitfalls of Polygenic Risk Scores
Polygenic risk scores could personalize healthcare, but fairness, evidence and ethics must guide their use.
Advances in genetics have made it possible to analyze thousands of genes at once, producing scores that estimate disease risk with high precision. But are polygenic risk scores ready to transform healthcare, or do their limitations demand caution?
Technology Networks spoke with Dr. Anna CF Lewis, a bioethicist focused on researching the ethical, legal and social implications of genomics at Harvard Medical School, to explore the promise and the challenges of polygenic risk scores.
Understanding polygenic risk scores and their potential
Genetic research has aimed to understand why some people are more likely to develop certain diseases than others. One emerging tool in this effort is the polygenic risk score.
“A polygenic risk score is a numerical estimate of an individual’s genetic predisposition to a complex disease. The score is calculated by aggregating the effects of many genetic variants, typically single-nucleotide variants,” said Lewis.
Unlike genetic tests that focus on a single mutation, a polygenic risk score considers the small contributions of thousands, or even millions, of genetic variants across the genome. Each variant is assigned a weight based on how strongly it has been linked to a particular disease in large population studies. When combined, these weights produce a score that estimates an individual’s overall genetic risk relative to the general population.
For instance, researchers have developed a polygenic risk score that estimates an individual’s lifetime risk for coronary artery disease.
The excitement around polygenic risk scores comes from their potential to personalize healthcare and guide preventive strategies. If doctors and patients can identify individuals at higher genetic risk for conditions such as heart disease or diabetes, they could intervene earlier with lifestyle changes, screenings or preventive treatments.
“It is hoped that polygenic risk scores can identify the most effective ways to incorporate their use into healthcare,” said Lewis. “Though research is still underway to determine the extent to which this hope is borne out.”
While the science is promising, it remains an evolving field, and researchers continue to refine these scores, aiming to understand exactly how best to translate genetic insights into meaningful health outcomes.
Ethical and practical challenges in using polygenic risk scores
While polygenic risk scores hold promise for personalizing healthcare, they also raise ethical and practical challenges.
“One issue that is often raised is the inconsistent performance across populations. The scores work best for individuals well represented in the training data, and that is skewed to white individuals,” said Lewis.
This disparity highlights a larger question: even if the scores are statistically accurate, how and where can they genuinely improve lives? Lewis emphasizes that predictive performance is just one piece of a much bigger picture:
“I personally think the bigger challenge is working out the contexts where these scores will actually improve lives the most. We really need to think about the whole process by which someone benefits.”
“Predictive performance matters, but so does which conditions to focus on, what follow-up actions are available for those identified as at higher risk and how the scores are integrated into care. At all of those stages, and not just predictive performance, there are questions of fairness,” she added.
“An additional issue is that we need scores that are more reliable for an individual. Right now, different scores will give very different answers for an individual,” said Lewis, which raised questions about consistency and trustworthiness.
Beyond technical limitations, the question of clinical utility is central to ongoing debates among stakeholders. Clinicians, patients and policymakers are less divided by perspective than by evidence.
“The main current difference is not between these different groups; it is whether these scores have, or will demonstrate, clinical utility,” Lewis explained.
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“Prospectively gathered evidence, which reflects not just the sharing of risk information, but also an understanding of how that information is used, including whether it actually improves the outcomes we are hoping it will,” is needed.
The integration of polygenic risk scores into routine care requires careful evaluation, not only of predictive power but also of fairness, reliability and real-world effectiveness. Without this, the promise of polygenic risk scores remain largely theoretical.
Ethical challenges of polygenic risk scores on the horizon
As polygenic risk scores become more integrated into healthcare, new ethical concerns are likely to emerge. One major area of attention is the potential for genetic discrimination.
“We might see some more concerns about genetic discrimination from life insurers,” said Lewis, potentially creating inequalities for those identified as higher risk.
Another emerging concern is the use of polygenic risk scores in embryo selection, which could become more mainstream as genomic technologies advance, raising profound ethical questions about the limits of reproductive choice and societal pressure toward “genetic optimization.”
“We might need to think more carefully about how we use responsibility language. We need to keep our eye on genetic fatalism,” she added.
Lewis’s warning about genetic fatalism – the belief that one’s genes rigidly determine health outcomes – underscores the broader challenge: even as scientific tools advance, ethical reflection must keep pace.
How we discuss risk, responsibility and prevention will shape whether these powerful technologies benefit society equitably or exacerbate existing inequalities.
The ethical landscape of polygenic risk scores will continue to evolve alongside their scientific adoption. Proactive engagement, transparency and careful policy development will be essential to ensure that these scores enhance, rather than limit, individual and societal well-being.
