Genetic subtyping of obesity reveals biological insights into the uncoupling of adiposity from its cardiometabolic comorbidities (2025) Nathalie Chami

Description

This study conducted a multi-trait genome-wide association analysis (GWAS) using data from 452,768 UK Biobank participants to examine obesity heterogeneity in relation to cardiometabolic health. Researchers identified 266 variants associated with continuous ‘uncoupling phenotypes’ (ranging from high adiposity with healthy cardiometabolic profiles to low adiposity with unhealthy ones). These variants formed eight distinct genetic subtypes of obesity, revealing mechanisms that uncouple obesity from cardiometabolic comorbidities, which is intended to support precision medicine.