Doctors uncover genetic clues as to why obesity affects people differently

Doctors have long warned that carrying excess weight can increase the risk of serious conditions such as type 2 diabetes, heart disease and high blood pressure

But new research suggests the picture is more complex. While obesity is dangerous for most, not everyone faces the same risks.

Scientists have discovered genetic differences that help explain why some people with obesity remain relatively healthy, while others develop serious conditions such as diabetes and heart disease.

A large-scale study from the Icahn School of Medicine at Mount Sinai in New York and the University of Copenhagen analysed genetic data from more than 450,000  people of European ancestry.

The team compared body fat levels with markers of metabolic health, such as blood pressure, cholesterol and blood sugar.

They found 266 genetic variants that appeared to “uncouple” obesity from disease risk. In other words, people carrying these variants were more likely to put on weight but less likely to show the warning signs of metabolic illness. 

Researchers say the new findings could eventually change how we predict, prevent, and treat obesity and its complications.

“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,” said Nathalie Chami, the first author on this paper and instructor of environmental Medicine, and artificial intelligence and human health, at the Icahn School of Medicine.

Obesity is not a single condition

The research identified eight distinct obesity subtypes, each linked to unique health risks.

“By uncovering these genetic differences, we can start to understand why obesity leads to different health outcomes in different individuals,” said Chami.

 “Obesity is not a single condition. It is made up of different subtypes, each with its own risks,” Chami added.

The research also found that the effects of these protective variants that reduce disease risk were already visible in children. 

Kids carrying the protective variants were more likely to develop obesity, but did not show the expected warning signs of metabolic disease.

The researchers now plan to study more diverse populations to look for new genes that influence body fat but are not tied to related conditions such as diabetes or heart disease. 

They will do this by examining measures of body fat alongside key indicators such as cholesterol levels, blood sugar control and blood pressure.

However, it cautions that the findings do not mean obesity is harmless.

“Most people with obesity still face health challenges, and lifestyle factors such as diet and exercise remain critical for overall health,” said Zhe Wang, the co-first author on this paper, and adjunct assistant professor of artificial intelligence and human health at the Icahn School of Medicine, and assistant Professor at the University of Alabama in Birmingham.

According to the World Health Organization (WHO), in 2022, one in eight people in the world was living with obesity. Worldwide adult obesity has more than doubled since 1990, and adolescent obesity has quadrupled, the organisation said.