Development and validation of a trans-ancestry polygenic risk score for type 1 diabetes
Authors' conclusion
We developed a trans-ancestry PRS that outperformed the European-based GRS2x. Importantly, TA-PS provides a comparable prediction in various ancestries, which supports its use in population-wide screening programmes.
Study context
- Population
- Multi-ancestry T1D case-control cohort from Montreal, Canada; validation in CHOP-CAG, GRACE, All of Us and UK Biobank556 non-European
- Participants
- 4,657 participants
- Comparison
- Trans-ancestry PRS vs European-based GRS2x
- Outcome
- Discrimination (AUROC), sensitivity and specificity for T1D
Methodological detailsdevelopment and validation, multi-ancestry case-control cohort, external validation in two case-control and two population-based cohorts, Developed with PRS-CSx using European, East Asian, African American and Hispanic T1D GWAS data (29,469 cases)
- Development and validation
- Multi-ancestry case-control cohort
- External validation in two case-control and two population-based cohorts
- Developed with PRS-CSx using European, East Asian, African American and Hispanic T1D GWAS data (29,469 cases)
Performance
As reported in the abstract
AUROC, multi-ancestry Montreal cohort
| Test or model | Area under the receiver operating curve (AUROC) |
|---|---|
| Trans-ancestry PRS (TA-PS) | 0.89 |
| GRS2x | 0.85 |
Area under the receiver operating curve (AUROC)
Trans-ancestry PRS (TA-PS)0.89
GRS2x0.85
Further findings
| Outcome | TA-PS | GRS2x |
|---|---|---|
| Sensitivity at 90th percentile cut-off | ||
| Sensitivity, Europeans | 0.71 | 0.56 |
| Sensitivity, South Asians | 0.77 | — not stated in the abstract |
| Sensitivity, African Americans | — not stated in the abstract | 0.32 |
| Specificity | ||
| Specificity, all ancestries | ≥0.83 | — not stated in the abstract |
— not stated in the abstract
Sensitivity at 90th percentile cut-off
- Better overall sensitivity with TA-PS
Specificity
- Specificity with TA-PS slightly lower than GRS2x, still acceptable
External validation
- Results validated in the four independent cohorts
Original publication
Development and validation of a trans-ancestry polygenic risk score for type 1 diabetes. Diabetologia. Published 7 March 2026. doi:10.
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