Not everyone who is obese faces the same health risks, and a new study suggests that genes may explain why. An international team of researchers from the Icahn School of Medicine at Mount Sinai and the University of Copenhagen examined genetic data of 452,768 people and found variants in 205 regions of the genome that are linked to higher body fat but better metabolic health.
Based on these findings, the scientists created a genetic risk score to measure the combined impact of these variants. People with higher scores were more likely to develop obesity but were less likely to suffer from complications such as diabetes, high blood pressure, high cholesterol, or heart disease.
The results suggest that the way fat cells function in different individuals plays a key role in determining whether obesity leads to related illnesses.
The protective genetic effects were also seen in children. Those carrying the variants were more likely to become obese but did not show the usual warning signs of metabolic disease. The study, published in Nature Medicine, further identified eight subtypes of obesity, each associated with distinct health risks.
The researchers noted that these discoveries could help doctors predict which patients are more vulnerable to complications and guide the development of new treatments that copy the protective genetic effects. They also cautioned that obesity is not without risk, as lifestyle factors like diet and exercise remain important for overall health.
The study was carried out using data from the UK Biobank, which includes people of European ancestry. The researchers plan to extend the work to more diverse populations. They analysed multiple traits related to body fat and cardiometabolic conditions, including lipid, glycemic, and blood pressure traits, to identify genes that influence obesity without being tied to related diseases.
By highlighting biological pathways that separate obesity from its usual complications, the findings are expected to support more personalised care, targeted therapies, and early prevention strategies, even beginning in childhood.
