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Prioritizing the detection of rare pathogenic variants in population screening

Nature Reviews Genetics volume 24, pages 205–206 (2023)Cite this article

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Population genomic screening to detect carriers of rare monogenic variants for medically actionable conditions is supported by substantial evidence of clinical utility and cost effectiveness. Much less evidence supports screening by polygenic risk scores, which do not detect rare variants. Using only polygenic scores in population screening initiatives, while ignoring the detection of higher-risk rare monogenic variants, is ill-advised.

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Acknowledgements

The authors thank J. Tiller for her input into this article. P.L. is supported by a National Heart Foundation Future Leader Fellowship (102604) and grants from the Australian Government Department of Health, Medical Research Future Fund, Genomics Health Futures Mission (APP2009024) and National Institutes of Health (1127060). R.M. is funded by the Yorkshire Cancer Research and Eve Appeal into Population testing and has been supported by an NHS Innovation Accelerator (NIA) Fellowship for population testing. R.C.G. is funded by NIH grants: TR003201, HG008685, HL143295, OD026553 and by the Franca Sozzani Fund for Preventive Genomics.

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Author notes

  1. These authors contributed equally: Ranjit Manchanda & Robert C. Green.

Authors and Affiliations

  1. Public Health Genomics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia

    Paul Lacaze

  2. Wolfson Institute of Population Health, CRUK Barts Centre, Queen Mary University of London, London, UK

    Ranjit Manchanda

  3. Department of Gynaecological Oncology, St Bartholomew’s Hospital, London, UK

    Ranjit Manchanda

  4. Department of Health Services Research, Faculty of Public Health & Policy, London School of Hygiene & Tropical Medicine, London, UK

    Ranjit Manchanda

  5. Mass General Brigham, Broad Institute, Ariadne Labs and Harvard Medical School, Boston, MA, USA

    Robert C. Green

Authors
  1. Paul Lacaze
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  2. Ranjit Manchanda
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  3. Robert C. Green
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Contributions

The authors contributed equally to all aspects of the manuscript.

Corresponding author

Correspondence to Paul Lacaze.

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Competing interests

R.M. declares advisory board membership from Astrazeneca/MSD/EGL/GSK. R.C.G. has received compensation for advising Allelica, Fabric, GenomeWeb, Genomic Life and Verily; and is a co-founder of Genome Medical and Nurture Genomics. P.L. declares no competing interests.

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Our Future Health: https://ourfuturehealth.org.uk/research-programme/

PROTECT: https://www.qmul.ac.uk/wiph/news/latest-news/items/31-million-for-protect-trial-population-based-genetic-testing-for-cancer-risk-in-women.html

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Lacaze, P., Manchanda, R. & Green, R.C. Prioritizing the detection of rare pathogenic variants in population screening. Nat Rev Genet 24, 205–206 (2023). https://doi.org/10.1038/s41576-022-00571-9

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  • DOI: https://doi.org/10.1038/s41576-022-00571-9

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