Genetic Clues Explain Why Obesity Affects People Differently

Ever wondered why some people with obesity remain relatively healthy while others develop serious conditions like diabetes and heart disease?

An international team of researchers, led by the Icahn School of Medicine at Mount Sinai and the University of Copenhagen, has uncovered key genetic factors that help explain this difference. Their study, published in Nature Medicine, offers new insights into the complex nature of obesity.

The researchers analyzed genetic data from over 450,000 individuals and identified variants in 205 regions of the genome linked to higher body fat but better metabolic health. Using these findings, they developed a genetic risk score that predicts who is more likely to become obese but less likely to suffer from complications such as high blood pressure, high cholesterol, diabetes, or heart disease. This difference is partly due to how fat cells function differently in various people.

Importantly, these protective genetic effects were also observed in children. Children carrying these genetic variants were more prone to obesity but did not show typical warning signs of metabolic disease.

“Our study shows that obesity is not a single condition — it has multiple subtypes, each with distinct risks,” said Dr. Nathalie Chami, the study’s first author. “Understanding these genetic differences can transform how we predict, prevent, and treat obesity and its complications.”

The team identified eight different obesity subtypes, each linked to unique health risks. These insights could help doctors identify patients most at risk and develop new treatments that replicate the protective effects found in some individuals.

However, the researchers caution that obesity remains a serious health concern. “Most people with obesity still face health challenges, and lifestyle factors such as diet and exercise remain crucial,” said Dr. Zhe Wang, co–first author.

The study focused on individuals of European ancestry from the UK Biobank, with plans to extend research to more diverse populations.

By mapping new biological pathways that separate obesity from related diseases, the findings could lead to more personalized treatments and earlier prevention — even starting in childhood, said Dr. Ruth Loos, the study’s corresponding author.