Josep Mercader, PhD

Alicia Huerta-Chagoya, PhD

Polygenic risk scores (PRS) can help identify individuals who are at heightened risk for conditions like type 2 diabetes (T2D), where many genetic risk factors may contribute to susceptibility.

However, because most PRS to date have been built on data from European populations, they tend to perform better for people of this ancestry than others.

The goal of a recent international study, headed by investigators at Mass General Brigham, Vanderbilt University Medical Center and the Broad Institute, was to improve genetic prediction of T2D across diverse global populations.

The team—led by Alicia Huerta-Chagoya, PhD, and Joohyun Kim, PhD, as first authors, and Josep Mercader, PhD, and Maggie C.Y. Ng, PhD, as senior authors—developed PRS based on genetic data harmonized across five ancestry groups. More than 360,000 T2D cases and 1.8 million controls were integrated, with over 40% representation from non-European populations.

Not only was this one of the largest and most diverse genetic datasets ever assembled for this purpose, but the resulting scores consistently outperformed previously published scores across all five studied population groups. Individuals at the highest genetic risk had a three- to seven-fold higher risk of developing T2D, and higher genetic risk was also linked to earlier disease onset and greater risk of microvascular complications.

Importantly, the newly derived PRS identified people who were at risk even among those who had normal blood sugar levels. Overall, the work represents an important advance toward more equitable and generalizable genetic risk prediction for diabetes.

Published in Lancet Diabetes and Endocrinology on April 27, 2026 | Read the paper: “Multi-ancestry polygenic risk scores for the prediction of type 2 diabetes and complications in diverse ancestries”

Summary reviewed by: Alicia Huerta-Chagoya, PhD; Josep Mercader, PhD