Study highlights overdiagnosis risk in newborn genome screening

Researchers at the University of Exeter are urging caution over the growing use of genome screening in newborn babies, after large-scale population studies suggested the approach could lead to significant overdiagnosis and unnecessary concern for families.

Presented at the European Human Genetics Conference and published in the European Journal of Human Genetics, the research examined whether genetic variants previously linked to serious disease carry the same level of risk when identified through population-wide screening programmes. The findings suggest that, in many cases, disease risk may be considerably lower than earlier studies have indicated.

Newborn genome screening programmes, now being piloted in countries including the United Kingdom, involve sequencing an infant’s entire genetic code to identify hundreds of potentially treatable conditions. However, researchers warn that much of the current understanding of genetic risk is based on studies of already-diagnosed patients or high-risk families, which may overestimate disease likelihood in the wider population.

To test this, the Exeter team analysed genetic data from almost one million volunteers in large population cohorts including UK Biobank and All of Us Research Program. Focusing on more than 50 genes linked to 15 diseases included in current screening studies, the researchers assessed whether carriers of specific variants actually developed disease.

The analysis found that the greatest risk of overdiagnosis occurred in conditions where disease is driven by changes in a single copy of a gene, raising concerns that screening could identify infants as high risk even if they may never develop symptoms.

Dr Leigh Jackson of the University of Exeter Medical School said the findings indicate that genetic variants often carry a weaker association with disease than previously thought, underlining the need to reassess risk estimates before expanding newborn screening programmes.

Professor Caroline Wright added that while newborn genome screening has major potential to improve healthcare, stronger evidence is needed to ensure families are not exposed to unnecessary anxiety or inappropriate intervention.

The researchers conclude that further studies are required before large-scale implementation of newborn genome screening, ensuring benefits are delivered without unintended harm.

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