Telling parents their newborn carries high disease risk has profound impact
At the University of Exeter, researchers have uncovered a quiet but consequential flaw at the heart of newborn genome screening: the risk estimates guiding these programs were built from studies of the already-sick, not the general population, making rare variants appear far more threatening than they truly are. Analyzing nearly a million volunteers, the team found that genetic links to disease are often much weaker in healthy populations than prior research suggested. The concern is not with the technology itself, but with the speed at which it is being deployed before our understanding has caught up — because a misread genome handed to new parents is not merely a data error, it is the beginning of a story that may never needed to be told.
- Newborn genome screening programs are expanding rapidly across the UK and beyond, carrying the promise of catching treatable diseases early — but built on risk estimates that may be fundamentally inflated.
- Because most genetic research draws from people already diagnosed or from high-risk families, the perceived danger of certain variants is far greater than what appears in the broader, healthy population.
- When these overestimated risks are applied to healthy newborns with no family history, the result can be a cascade of false alarms — parents told their child faces serious disease that may never arrive.
- The psychological toll on families receiving inaccurate high-risk diagnoses is severe: unnecessary medical interventions, chronic anxiety, and childhoods lived under the shadow of a condition that may never materialize.
- The Exeter team, publishing across multiple papers and presenting at the European Human Genetics Conference, is not calling for a halt — they are calling for precision, urging that accurate, population-level risk data must precede any widespread rollout.
Researchers at the University of Exeter have spent months analyzing genetic data from nearly a million people, and what they found carries serious implications for how we screen newborns for disease. The problem, they say, is deceptively simple: we have been overestimating how often genetic variants actually cause illness.
Most genetic research has been conducted on people who already have a condition or come from families known to carry it. In that context, a mutation looks far more dangerous than it is in the general population. When those inflated estimates are applied to newborn screening — testing healthy babies with no family history — the result is a wave of false alarms that can devastate families before a child has taken its first steps into the world.
Dr. Leigh Jackson and his team examined more than fifty genes linked to fifteen diseases now included in large-scale screening trials. When they looked at what actually happened to carriers of these variants in the UK Biobank and the All of Us research cohort, the genetic link to disease was present — but far weaker than previous studies had suggested. The overdiagnosis risk was sharpest for conditions requiring the loss of just one gene copy, where real-world population risk often falls well below what family-based studies imply.
Professor Caroline Wright framed the human stakes plainly: telling parents their newborn carries a high risk of serious disease has a profound psychological impact. It can trigger unnecessary interventions and cast a long shadow over a childhood — for a diagnosis that may never materialize.
The researchers are not arguing against newborn genome screening. They are arguing for it to be done carefully. Before these programs scale up, they say, we need risk estimates grounded in healthy, general populations — because the cost of getting it wrong is not only medical. It is deeply human.
A team of researchers at the University of Exeter has spent months combing through genetic data on nearly a million people, looking for a problem that could reshape how we screen newborns for disease. What they found should give pause to anyone planning to sequence a baby's entire genome and hunt through it for hundreds of potential conditions.
The issue is deceptively simple: we have been overestimating how often genetic variants actually cause disease. Most genetic research to date has been conducted on people who already have a condition, or who come from families known to carry it. In that context, a particular genetic mutation looks far more dangerous than it actually is in the general population. When those inflated risk estimates get applied to newborn screening—where you're testing healthy babies with no family history—the result is a cascade of false alarms that can devastate families.
Dr. Leigh Jackson, working at the University of Exeter Medical School, explained the disconnect plainly. The team analyzed more than fifty genes linked to fifteen diseases that are now being included in large-scale newborn screening trials. When they looked at what actually happened to people in the general population who carried these variants—people in UK Biobank and the All of Us research cohort—the picture changed. The genetic link to disease was there, but it was weaker than previous studies had suggested. Much weaker, in many cases.
The research, funded by the Medical Research Council and the National Institute for Health and Care Research, has produced three papers already published in the European Journal of Human Genetics, with two more in preprint. The findings are being presented at the European Human Genetics Conference this month. They paint a cautionary portrait of a technology that is spreading faster than our understanding of it.
The biggest risk of overdiagnosis, the team found, occurs when a disease requires the loss of just one copy of a gene—a scenario where the actual risk in the general population is often far lower than studies of affected families would suggest. For conditions where both copies of a gene must be lost to cause disease, the picture is more mixed, though their forthcoming research suggests the overdiagnosis risk remains real.
Professor Caroline Wright, also at the University of Exeter Medical School, framed the stakes clearly. The UK is leading the world in newborn genome screening, and other countries are watching to see how it unfolds. The potential benefits are genuine—catching treatable genetic diseases early could save lives and prevent suffering. But there is a cost to getting it wrong. Telling parents that their newborn carries a high risk of developing serious disease has a profound psychological impact. It can trigger unnecessary medical interventions, endless worry, and a childhood shadowed by a diagnosis that may never materialize.
The researchers are not arguing against newborn genome screening. They are arguing for it to be done carefully, with the most accurate risk estimates available. Before these programs are rolled out at scale, they say, we need better evidence. We need to know, with precision, what these genetic variants actually mean when they appear in a healthy baby born to parents with no family history of disease. Until we have that knowledge, the risk is not just medical. It is human.
Notable Quotes
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.— Dr. Leigh Jackson, University of Exeter Medical School
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.— Professor Caroline Wright, University of Exeter Medical School
The Hearth Conversation Another angle on the story
Why does it matter so much where the original genetic research came from? Isn't a disease-causing variant still disease-causing?
Not in the way that matters for screening. If you study only people who have the disease, you're looking at the worst-case scenarios. You're missing all the people who carry the same variant and never get sick. That changes the math entirely.
So the researchers found that these variants are less dangerous than we thought?
In the general population, yes. When you look at a million unselected people, the actual risk is often much lower than studies of affected families suggested. That's the gap they're trying to close.
What happens to a family if they get a false alarm from newborn screening?
They're told their baby is at high risk of a serious disease. That news doesn't just sit in your head neutrally. It shapes how you parent, what medical care you pursue, how you see your child. If the risk was overstated, you've caused real harm.
Is the UK program going to stop while they gather more data?
That's the question. The researchers are saying we need better evidence before rolling this out widely. The UK is leading the way, so what happens here will influence how other countries approach it.
What would better evidence look like?
Exactly what they're doing now—testing these genetic variants in large, unselected populations and seeing what actually happens. Not in people who are already sick, but in everyone.