For Immediate Release: Wednesday, October 21, 2026, 2:50 p.m. U.S. Eastern Time
Media Contact: Evelyn Mantegani, +1 240-833-2014, [email protected]
Presented By: Sohail Zahid, MD, PhD, Johns Hopkins University
Rockville, Md. – Body mass index, or BMI, has long served as a standard measure of obesity, but it does not directly account for how excess body fat affects organ function and overall health. In the first genome-wide analysis based on a new definition of clinical obesity, researchers identified genetic signals that differed substantially from those associated with BMI and showed stronger connections to cardiovascular health.
Researchers at Johns Hopkins University analyzed 151,642 people with clinical obesity and 128,874 controls without obesity from the All of Us Research Program and UK Biobank, spanning five ancestry groups. They identified 127 independent genetic loci associated with clinical obesity. Of these, 63 had no significant association with BMI. One of the most discordant variants was located in the LPL gene, which encodes lipoprotein lipase and was associated with elevated triglyceride levels.
The team also developed a clinical obesity polygenic score, which combines information from many genetic variants. Compared with a BMI-based polygenic score, the new score showed stronger associations with cardiovascular risk factors and protein markers related to inflammation and insulin resistance. It also improved risk discrimination for myocardial infarction, heart failure, and stroke. Researchers validated the improvement across four additional long-running U.S. studies.
The findings suggest that defining obesity through excess body fat and related organ dysfunction may reveal biologically and clinically relevant risks that BMI alone does not capture. Although the score is not yet ready for clinical implementation, the study represents a step toward more precise assessment of obesity-related cardiovascular risk.
About the American Society of Human Genetics (ASHG)
The American Society of Human Genetics (ASHG) is the leading global organization advancing the science of human genetics and genomics. Representing nearly 8,000 researchers, clinicians, genetic counselors, educators, and other professionals, ASHG drives progress in understanding the human genome and its role in health and disease. The Society fosters innovation and collaboration through its flagship events and publications—including the ASHG Annual Meeting and its peer-reviewed journals The American Journal of Human Genetics and Human Genetics and Genomics Advances. ASHG also champions science advocacy, supports the next generation of genetics professionals, and promotes responsible policies and public engagement in genetics. Learn more at www.ashg.org.
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