A Polygenic Score for Type 2 Diabetes Improves Risk Stratification Beyond Current Clinical Screening Factors in an...

Area of Science:

• Genetics
• Endocrinology
• Public Health

Background:

• Current type 2 diabetes (T2D) screening relies on age, family history, and BMI, missing many undiagnosed adults.
• There is a need for improved screening tools to identify high-risk individuals more effectively.

Purpose of the Study:

• To evaluate a polygenic score (PGS) for type 2 diabetes (T2D) as a complementary screening tool.
• To assess the PGS's predictive utility for T2D onset, prediabetes, and disease progression.
• To determine the PGS's effectiveness across diverse ancestral groups.

Main Methods:

• Developed and validated a T2D-specific polygenic score (PGS).
• Assessed PGS predictive performance against traditional risk factors (age, family history, BMI).
• Analyzed PGS association with age of onset, prediabetes, incident T2D, and clinical outcomes in European and Hispanic/Latino cohorts.

Main Results:

• The T2D PGS independently predicted T2D risk and improved prediction when combined with family history.
• Higher PGS was associated with earlier T2D onset (–1.3 years/SD) and increased odds of prediabetes (+23%/SD).
• The PGS showed predictive value across European and Hispanic/Latino populations, including for age of onset and prediabetes.

Conclusions:

• A T2D polygenic score (PGS) can enhance current screening practices by identifying high-risk individuals.
• The PGS offers valuable risk stratification and prediction of disease progression and early onset.
• The T2D PGS demonstrates clinical utility across diverse ancestries, supporting broader application in diabetes management.