A research team at the University of Exeter is raising a red flag on newborn genome screening, saying further studies are needed to reduce risks from overdiagnosis.
Newborn genome screening pilot studies, which are increasingly being rolled out in multiple countries, involve determining the entire sequence of a baby’s genetic code and interrogating it for hundreds of potentially treatable conditions.
The UK research team cautions that most genetic studies to date have been carried out in groups of people who already have a condition or are in a high-risk family. This means that the known risk of a genetic variant causing a disease is often higher than the actual risk in the general population.
To put this to the test, the Exeter team analyzed genetic variants previously found to cause disease using large datasets of the general population, including nearly 1 million volunteers in either UK Biobank or All of Us. Focusing on more than 50 genes across 15 diseases included in large scale trials for newborn genome screening, the team looked for the variants, and whether people who carry them have the disease.
In most cases, although the team found a link between the genetic variants and the disease, it was much weaker than previous research suggested. The published research found that the biggest risk of overdiagnosis arose when the risk of disease stems from a loss of just one of the two copies of a gene. However, the picture was mixed—and for other conditions, their upcoming research will show that where both copies of the gene need to be lost to cause disease, the evidence suggests a lower risk of overdiagnosis.
“The UK is leading the way on newborn genome screening and the world is watching. We urgently need the best evidence to ensure we get this right,” said study author Caroline Wright of the University of Exeter Medical School. “The benefits of a successful program will be profound, but we need to be aware of the risk of overdiagnosis based on current evidence. Being told your baby is at high risk of developing disease has a massive impact on families—we need to ensure we use the most accurate risk estimates possible to provide the best care.”
Data from University of Exeter