CBMR scientists discover protective genes that keep some people with obesity healthy

 People are normally diagnosed with obesity by measuring BMI, a person’s height-to-weight ratio. However, scientists have long understood that two people with obesity, and the same high BMI, do not necessarily live with the same health risks. So why do some people appear to be protected, while others face a higher risk of heart disease, diabetes and other cardiometabolic disorders?

Together with a team of international researchers, CBMR’s Loos Group set out to understand why obesity does not affect everyone in the same way. In a new study in the journal Nature Medicine, they have identified genetic differences that help explain why some people with obesity remain relatively healthy while others develop serious health conditions.

“Obesity is often treated as a single condition, but our study shows it's far more complex. People with the same BMI can have vastly different health outcomes: some develop serious conditions like diabetes and heart disease, while others remain relatively healthy,” says Professor Ruth Loos, senior author of the study.

“While these findings are promising, they don’t mean obesity is harmless. Lifestyle factors remain critical, and most people with obesity still face health challenges. This work lays the foundation for precision medicine in obesity care—and we’re just getting started.”

 Genetic protection visible even in childhood

The team analyzed genetic data from nearly half a million people and discovered genetic variants in 205 regions of the genome linked to higher body fat but better metabolic health. Using these discoveries, they developed a genetic risk score that adds up the impact of these variants. Individuals with higher scores were more likely to develop obesity, but were less likely to suffer from complications such as high blood pressure, high cholesterol, diabetes, or heart disease.

Importantly, these protective genetic effects were already visible in children. Those carrying the protective variants were more likely to develop obesity, but did not show the expected warning signs of metabolic disease.

The research also identified eight distinct obesity subtypes, each linked to unique health risks. These insights could eventually help doctors predict which patients are most vulnerable to complications and inform new treatments that mimic the protective genetic effects found in some people.

 Paving the way for precision medicine approaches

The study was conducted in individuals from the UK Biobank, comprised of people from European ancestry, and future work will extend to more diverse populations. It leveraged this data to perform a comprehensive multi-trait genome-wide screen. The team wanted to find new genes that affect body fat without being linked to cardiometabolic comorbidities by analyzing three adiposity and eight cardiometabolic traits, including lipid, glycemic, and blood pressure traits.

“By uncovering these genetic differences, we can start to understand why some people develop serious health problems while others do not. This could eventually change how we predict, prevent, and treat obesity and its complications,” said Nathalie Chami, co-lead author of the research, and Instructor of Environmental Medicine, at Icahn School of Medicine at Mount Sinai.

Read the paper here.