New Genetic Risk Score Better Predicts Diabetes, Obesity, and Related Health Risks
A newly developed genetic risk score (PRS) is demonstrating improved accuracy in predicting the development of type 2 diabetes (T2D) and obesity, as well as the potential for downstream health complications. Researchers from Mass General Brigham have created these metabolic PRSs by integrating genetic data from some of the world’s largest biobanks, outperforming existing prediction models.
Understanding Polygenic Risk Scores
Type 2 diabetes and obesity are complex metabolic conditions influenced by a multitude of factors, including genetics. A polygenic risk score assesses an individual’s genetic predisposition to a disease by considering the combined effect of many genetic variants. This provides a more comprehensive estimate of risk than looking at individual genes in isolation. Mass General Brigham
How the New PRS Was Developed
The researchers built metabolic PRSs specifically for obesity and T2D. These scores go beyond traditional metrics like body mass index (BMI) and focus on genes associated with 20 different traits related to metabolic function, including fat distribution, insulin control, and glucose regulation. The development utilized genome-wide association studies (GWAS) encompassing data from over 8.5 million participants globally.
Improved Prediction of Clinical Outcomes
The new PRS not only predicts the likelihood of developing obesity or diabetes but also forecasts potential health consequences. Individuals identified as high-risk by the PRS were approximately twice as likely to require interventions like GLP-1 agonist medications or bariatric surgery compared to those with mid-range scores, over a median follow-up period of 5.5 years. Mass General Brigham
Enhanced Accuracy Across Diverse Populations
A key strength of this new PRS is its improved performance across different ancestral groups. By incorporating multi-ancestry GWAS data, with a particular emphasis on non-European populations, the researchers created risk scores that are more accurate for individuals of African, East Asian, and South Asian descent.
Future Directions and Clinical Implications
Researchers aim to further refine their understanding of the genetic subtypes of T2D and obesity to personalize patient classification and treatment strategies. The goal is to move beyond relying solely on BMI and consider underlying genetic susceptibility when assessing metabolic health.
“Early identification of people who are likely to have a worse trajectory of poor metabolic health, before they even develop these conditions, can help us improve prevention and clinical interventions,” said Akl Fahed, MD, MPH, of the Cardiovascular Research Center at Massachusetts General Hospital. Mass General Brigham
GLP-1 Medication Coverage Updates
Mass General Brigham Health Plan is updating its coverage of GLP-1 medications. While coverage will continue for type 2 diabetes, it will no longer include GLP-1s for weight management, beginning January 1, 2026. The health plan offers programs like “Healthier You” and access to health coaches to support members in their weight loss and wellness journeys. Mass General Brigham Health Plan
Source: Kim, M. S., et al. (2026). Metabolic polygenic risk scores for prediction of obesity, type 2 diabetes, and related morbidities. Cell Metabolism. DOI: 10.1016/j.cmet.2026.02.009.