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Psychological and behavioural considerations for integrating polygenic risk scores for disease into clinical practice

Nature Human Behaviour volume 9, pages 1098–1106 (2025)Cite this article

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Abstract

A polygenic risk score (PRS) summarizes in one number an individual’s estimated genetic association with a specific trait or disease based on the common DNA variants included in the score. Disease PRSs have the potential to positively affect population health by improving disease risk prediction, thereby also potentially improving disease prevention, early intervention and treatment. However, given the potential psychological, behavioural and other harms, there are also concerns about integrating PRSs into clinical tools and healthcare systems. Here we assess five arguments against implementing PRSs for physical disease in clinical practice that revolve around psychological and behavioural considerations. For each argument, we consider a counterargument, the evidence and underlying theory, any gaps in the evidence base and possible future directions and research priorities. We conclude that, although there may be other barriers to implementation, there is currently little evidence of psychological or behavioural harms from integrating PRSs into practice.

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Acknowledgements

We are grateful to C. Lewis and J. Waller for feedback on an early draft of this paper.

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Authors and Affiliations

  1. Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

    Saskia C. Sanderson

  2. Department of Behavioural Science and Health, University College London, London, UK

    Saskia C. Sanderson

  3. Mental Health Mission, National Institute for Health and Care Research (NIHR) Mental Health Translational Research Collaboration, London, UK

    Saskia C. Sanderson

  4. Public Health Genomics Foundation, Cambridge, UK

    Saskia C. Sanderson

  5. Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK

    Michael Inouye

  6. Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Hinxton, UK

    Michael Inouye

  7. Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia

    Michael Inouye

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S.C.S. and M.I. jointly developed the overall concept for the manuscript, wrote the initial manuscript and revised it based on reviewer and editorial feedback.

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Correspondence to Saskia C. Sanderson.

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Competing interests

M.I. is a trustee of the Public Health Genomics Foundation and a member of the Scientific Advisory Board of Open Targets. M.I. has research collaborations with AstraZeneca, Nightingale Health and Pfizer that are unrelated to this work. S.C.S. declares no competing interests.

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Sanderson, S.C., Inouye, M. Psychological and behavioural considerations for integrating polygenic risk scores for disease into clinical practice. Nat Hum Behav 9, 1098–1106 (2025). https://doi.org/10.1038/s41562-025-02200-x

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