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Maximizing cascade genetic testing for disease prevention through direct notification of at-risk relatives

Nature Medicine volume 31, pages 3225–3226 (2025)Cite this article

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Genomic medicine traditionally focuses on disease diagnosis and treatment. The historically high cost of genetic testing has precluded its availability at the population level, so that it has mostly been reserved for individuals with symptomatic disease. The use of genetic testing to identify those at high risk of preventable or treatable adult-onset disease — and to make interventions available before disease manifests—is less common. This is the new frontier of preventive medicine, and to harness its potential, we must maximize the identification of at-risk individuals in the population.

Cascade testing involves identifying and testing the at-risk relatives of an individual (the proband) who is found through DNA testing to have a genetic risk variant, as a way to increase the capacity to prevent disease in high-risk individuals, especially for medically actionable results. Maximizing the reach of cascade testing is the lowest-hanging fruit in the shift towards genomic disease prevention, with cascade testing uptake estimated at <50% of at-risk relatives1.

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Authors and Affiliations

  1. School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia

    Jane Tiller

  2. Centre for Law and Genetics, University of Tasmania, Hobart, Tasmania, Australia

    Margaret Otlowski

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  1. Jane Tiller
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  2. Margaret Otlowski
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Correspondence to Jane Tiller.

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J.T. led the discussions with the OAIC that led to the update to the privacy guidance discussed in the paper

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Tiller, J., Otlowski, M. Maximizing cascade genetic testing for disease prevention through direct notification of at-risk relatives. Nat Med 31, 3225–3226 (2025). https://doi.org/10.1038/s41591-025-03838-w

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