A study published in Nature Medicine has identified genetic differences that help explain why some individuals with obesity remain metabolically healthy, while others go on to develop serious health conditions like diabetes, highblood pressure, andheart disease. The research offers new insight into the biological complexity of obesity and its varied health consequences. Obesityis often treated as a single disease, but the study challenges this notion by analyzing genetic data from 452,768 individuals from the UK Biobank. Researchers discovered variants in 205 regions of the genome that were linked to higher levels of body fat, yet paradoxically, also to better metabolic health. By aggregating the impact of these variants, the team developed a genetic risk score that could predict who might develop obesity without the associated cardiometabolic complications. “Our study shows that obesity is not a single condition—it is made up of different subtypes, each with its own risks,” explained Nathalie Chami, PhD, first author and Instructor of Environmental Medicine and Artificial Intelligence and Human Health at the Icahn School of Medicine. The study also found that these protective genetic traits were already evident in children, suggesting early-life influences on long-term health outcomes. The researchers went on to identify eight distinct subtypes of obesity, each with its own health implications. However, the team emphasized that these findings do not make obesity risk-free. “Most people with obesity still face health challenges, and lifestyle factors such as diet and exercise remain critical for overall health,” noted Zhe Wang, PhD, co-first author of the study. By revealing new genetic pathways that separate obesity from its most dangerous complications, the research opens the door for more personalized and targeted approaches to managing obesity—starting as early as childhood. Reference:Chami, N., Wang, Z., Svenstrup, V. et al. Genetic subtyping of obesity reveals biological insights into the uncoupling of adiposity from its cardiometabolic comorbidities. Nat Med (2025). https://doi.org/10.1038/s41591-025-03931-0