Development and validation of a trans-ancestry polygenic risk score for type 1 diabetes - PubMed
4 days ago
- #polygenic risk score
- #trans-ancestry
- #type 1 diabetes
- Development of a trans-ancestry polygenic risk score (PRS) for type 1 diabetes to improve risk prediction across diverse populations.
- Utilization of PRS-CSx method and data from European, East Asian, African American, and Hispanic genome-wide association studies (total cases=29,469).
- Combination of a non-HLA component with over a million variants and the HLA component from a European PRS (GRS2x).
- Testing in a multi-ancestry cohort (N=4657) showed improved performance (AUROC=0.89) compared to GRS2x (AUROC=0.85).
- Better sensitivity at the 90th percentile cut-off with TA-PS (0.71 in Europeans, 0.77 in South Asians) vs. GRS2x (0.32 in African Americans, 0.56 in Europeans).
- Validation in independent cohorts (CHOP-CAG, GRACE, All of Us, UK Biobank) confirmed the effectiveness of TA-PS.
- TA-PS provides comparable prediction across ancestries, supporting its use in population-wide screening programs.