Genetic test predicts obesity in childhood

What if we could prevent people from developing obesity? The World Obesity Federation expects more than half the global population to develop overweight or obesity by 2035. However, treatment strategies such as lifestyle change, surgery and medications are not universally available or effective.

By drawing on genetic data from over five million people, an international team of researchers has created a genetic test called a polygenic risk score (PGS) that predicts adulthood obesity already in early childhood. This finding could help to identify children and adolescents at higher genetic risk of developing obesity, who could benefit from targeted preventative strategies, such as lifestyle interventions, at a younger age.

“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.

The study arises from the Genetic Investigation of Anthropometric Traits (GIANT) Consortium, an international collaboration of human genetics researchers dedicated to studying the genetic architecture of anthropometric traits such as human height and body mass index. The research involved a collaboration with the consumer genetics and research company 23andMe, inc., and the contributions of more than 600 scientists from 500 institutions, globally.

Twice as effective at predicting obesity as the next best test

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.

Genetics is not destiny

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.

Link to the study: https://www.nature.com/articles/s41591-025-03827-z