Uncovering Genetic Markers Driving Type 2 Diabetes Heterogeneity

A study on type 2 diabetes (T2D) pathophysiology reveals genetic heterogeneity in T2D development and complications. The research, involving over 2.5 million individuals of diverse ancestry, identified 1,289 T2D association signals and classified them into eight mechanistic clusters based on their cardiometabolic profiles. The study also uncovered ancestry-correlated heterogeneity in allelic effects at T2D association signals, with differences in mean BMI in T2D cases and controls across ancestry groups playing a role. Additionally, the study tested the association of cluster-specific polygenic scores with T2D-related vascular outcomes, providing insights into the genetic drivers of T2D heterogeneity.