Genetic Clues to Obesity's Varied Impact Revealed by Mount Sinai Study

An international research team has pinpointed genetic differences that help explain why some people with obesity remain relatively healthy while others develop serious conditions like diabetes and heart disease. The study, published in Nature Medicine, analyzed genetic data from 452,768 people and discovered variants in 205 regions of the genome linked to higher body fat but better metabolic health. The researchers developed a genetic risk score that adds up the impact of these variants, and 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.

Key Takeaways:

• The study, led by Icahn School of Medicine at Mount Sinai and the University of Copenhagen in Denmark, analyzed genetic data from 452,768 people and identified variants in 205 regions of the genome linked to higher body fat but better metabolic health.
• The research team developed a genetic risk score that adds up the impact of these variants, and 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.
• The study revealed eight distinct obesity subtypes, each linked to unique health risks, and the researchers caution that the findings do not mean obesity is harmless.
• Lifestyle factors such as diet and exercise remain critical for overall health, and the study's findings could eventually inform new treatments that mimic the protective genetic effects found in some people.
• The research team plans to extend their study to more diverse populations and hopes that the findings may pave the way for more personalized care, better-targeted therapies, and earlier prevention strategies, even from childhood.

Statistics:

• 452,768 people were included in the study, the largest genetic analysis of obesity and metabolic health conducted to date.
• The study identified 205 regions of the genome linked to higher body fat but better metabolic health, which could help understand why some people with obesity remain relatively healthy.
• Individuals with higher genetic risk scores were more likely to develop obesity (85.6% compared to 75.6% for those with lower scores), but were less likely to suffer from complications such as high blood pressure (43.1% vs. 58.5%), high cholesterol (31.4% vs. 42.1%), diabetes (22.2% vs. 35.4%), or heart disease (10.5% vs. 16.9%).
• The study revealed that the protective genetic effects were already visible in children, and kids carrying the protective variants were more likely to develop obesity but did not show the expected warning signs of metabolic disease.

Sources:

• Mount Sinai Health System. (2025). Mount Sinai Study Reveals Genetic Clues Explaining Why Obesity Affects People Differently. https://www.mountsinai.org/about/newsroom/2025/mount-sinai-study-reveals-genetic-clues-explaining-why-obesity-affects-people-differently
• DOI: 10.1038/s41591-025-03931-0