When researchers at the University of Exeter looked at genetic data from nearly one million everyday volunteers—not patients already known to be ill, but people living ordinary lives—they found something that could reshape how we think about newborn genome screening: the actual risk of disease from certain genetic variants is often lower than doctors have been telling new parents.
Newborn genome screening, which reads a baby's entire genetic code to check for hundreds of potentially treatable conditions, is expanding rapidly in countries including the UK. But a team at Exeter is urging caution, arguing that the evidence base needs to catch up before the technology is rolled out widely. Their research, presented at the European Human Genetics Conference and published across three papers in the European Journal of Human Genetics, draws on an unusually broad dataset—volunteers from both UK Biobank and the All of Us research program—to assess genetic risks in the general population rather than in people already known to have disease.
The team focused on more than 50 genes across 15 diseases currently included in large-scale newborn screening trials. For each gene variant, they asked a simple but previously overlooked question: do people who carry this variant in the general population actually develop the disease? The answer, across most cases, was less definitive than existing research suggested. "We found that in most cases, although there is a link between the genetic variants and the disease, it's weaker than previous research has suggested," said Dr. Leigh Jackson of the University of Exeter Medical School. "This is because most research is conducted in people who already have a disease or are at high risk. The actual risk is often lower if you're looking at the general population, as would be the case if you applied this risk to newborn screening."
The Exeter team identified one particular scenario—where disease risk stems from loss of just one copy of a gene pair—as carrying the highest potential for overdiagnosis. However, when both copies of a gene must be lost to cause disease, their findings suggest a lower risk of unnecessary alarm. The nuance matters enormously when you're telling new parents their baby might develop a serious illness.
"Being told your baby is at high risk of developing disease has a massive impact on families," said Professor Caroline Wright of Exeter Medical School. "We need to ensure we use the most accurate risk estimates possible in order to provide the best care." The team isn't arguing against newborn genome screening—they believe its benefits could be profound if done well. But they want larger population studies to refine the risk estimates before the program expands further. The UK is currently leading global efforts in this area, and the world is watching. Getting the evidence right now could spare countless families from anxiety rooted in numbers that don't reflect real-world outcomes.