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Promises under pressure: the modest predictive power of polygenic risk scores

European Journal of Human Genetics (2026)Cite this article

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A Correspondence to this article was published on 08 January 2026

The Original Article was published on 29 September 2025

Comment on a controversial topic in genomics and a response to: Roberts, E., Flaum, N. & Evans, D.G. Clinical implementation of polygenic risk scores. Eur J Hum Genet (2025). https://doi.org/10.1038/s41431-025-01931-9.

We read with interest the recent commentary by Roberts and colleagues on the clinical implementation of polygenic risk scores (PRS) [1]. While we welcome the enthusiasm for genomic tools in public health, we are concerned that several claims in the article overstate the clinical utility of PRS. Such framing risks misleading policymakers and clinicians about their readiness and transformative potential. Here, we outline evidence that PRS discrimination is generally weak, and their deployment in large-scale programmes is unlikely to yield the hoped-for impact on disease burden. This reflects a well-known paradox in epidemiology: a factor that is strongly associated with disease aetiology may nonetheless provide poor discrimination in a screening setting, because the strength of association does not inherently translate to high sensitivity and specificity [2].

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References

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Authors and Affiliations

  1. Centre for Human Genetics, University of Oxford, Oxford, UK

    Rachel Horton & Anneke Lucassen

  2. Centre for Personalised Medicine, University of Oxford, Oxford, UK

    Rachel Horton & Anneke Lucassen

  3. Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK

    Malcolm Dunlop

  4. Centre for Evidence and Values in healthcare, University of St Andrews, St Andrews, UK

    Margaret McCartney

  5. Dana-Farber Cancer Institute, Harvard University, Boston, USA

    Amit Sud

  6. Institute of Cancer Policy, King’s College London, London, UK

    Richard Sullivan

  7. Department of Oncology, University of Oxford, Oxford, UK

    Ian Tomlinson

  8. Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK

    Clare Turnbull & Richard Houlston

Authors
  1. Rachel Horton
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  2. Malcolm Dunlop
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  3. Margaret McCartney
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  4. Amit Sud
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  7. Clare Turnbull
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  8. Richard Houlston
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  9. Anneke Lucassen
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Contributions

All authors jointly conceived and designed this comment. RH led on the drafting of the comment and all other authors then contributed to revisions until consensus was reached and all approved the final version. AL is accountable for all aspects of the work.

Corresponding author

Correspondence to Anneke Lucassen.

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Horton, R., Dunlop, M., McCartney, M. et al. Promises under pressure: the modest predictive power of polygenic risk scores. Eur J Hum Genet (2026). https://doi.org/10.1038/s41431-025-01996-6

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