Scientists have developed a powerful genetic test that predicts whether a child as young as five is likely to become obese as an adult. Using data from over five million people, the tool—called a polygenic risk score—outperforms previous methods by a wide margin. It opens the door to early, targeted interventions. While genetics isn’t destiny, those with high risk responded well to lifestyle changes—though they also rebounded quickly when interventions stopped. The score is a major leap, though it’s still more accurate for people of European ancestry than others.
The Rising Tide of Obesity and a New Way to Predict It
What if it were possible to stop obesity before it starts? According to the World Obesity Federation, more than half of the global population is expected to have overweight or obesity by 2035. Yet, current treatment options—such as changes in diet and exercise, surgery, or medications—are not always accessible or effective for everyone.
Now, researchers have developed a genetic test using data from over five million people that can predict a person’s risk of becoming obese well before they reach adulthood. Known as a polygenic risk score (PGS), this test identifies children and teens who may be genetically predisposed to obesity. These individuals could benefit from early, targeted strategies such as lifestyle changes to help reduce their risk.
Early Prediction, Lifelong Impact
“What makes the score so powerful is its ability to predict, before the age of five, whether a child is likely to develop obesity in adulthood, well before other risk factors start to shape their weight later in childhood. Intervening at this point can have a huge impact,” says Assistant Professor Roelof Smit from the NNF Center for Basic Metabolic Research (CBMR) at the University of Copenhagen and lead author of the research published in Nature Medicine.
This work comes from the Genetic Investigation of Anthropometric Traits (GIANT) Consortium, a global network of genetics researchers focused on traits like height and body mass index. The study was carried out in partnership with 23andMe, inc., and included contributions from more than 600 scientists across 500 institutions worldwide.
Twice as Powerful: Breakthrough in Obesity Prediction
The subtle variations in our genomes can greatly impact our health. Thousands of genetic variants have been identified that increase our risk of obesity, for example, variants that act in the brain and influence our appetite. A PGS is like a calculator that combines the effects of the different risk variants that a person carries and provides an overall score.
To create their PGS, the scientists drew on the genetic data of more than five million people – the largest and most diverse genetic dataset ever. They then tested their new PGS for obesity on datasets of the physical and genetic characteristics of more than 500,000 people. They found that their new PGS was twice as effective as the previous best test at predicting a person’s risk of developing obesity.
“This new polygenic score is a dramatic improvement in predictive power and a leap forward in the genetic prediction of obesity risk, which brings us much closer to clinically useful genetic testing,” says Professor Ruth Loos from CBMR at the University of Copenhagen.
Genes, Weight Loss, and the Limits of Prediction
The scientists also investigated the relationship between a person’s genetic risk of obesity and the impact of lifestyle weight loss interventions, such as diet and exercise. They discovered that people with a higher genetic risk of obesity were more responsive to interventions but also regained weight more quickly when the interventions ended.
However, the new PGS has its limitations. Despite drawing on the genomes of a broader, more globally representative population, it was far better at predicting obesity in people with European-like ancestry than in people with African ancestry.
