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Other literature type . 2025
License: CC BY
Data sources: ZENODO
ZENODO
Other literature type . 2025
License: CC BY
Data sources: Datacite
ZENODO
Other literature type . 2025
License: CC BY
Data sources: Datacite
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Development and validation of a Trans-Ancestry polygenic risk score for Type 1 Diabetes

Authors: Jumentier, Basile;

Development and validation of a Trans-Ancestry polygenic risk score for Type 1 Diabetes

Abstract

Abstract Objectives The high heritability of type 1 diabetes has enabled the development of polygenic risk scores (PRS) as disease risk screening tools. PRS can identify individuals at the highest genetic risk in a population, who can benefit from autoantibody and metabolic surveillance, to avoid ketoacidosis at diagnosis and access preventive therapies. However, PRS for type 1 diabetes developed from European data perform less well in non-European ancestries. We aimed to develop a PRS with comparable performance among different ancestries. Methods Using a the PRS-CSx method, and data from large European, East-Asian, African-American and Hispanic type 1 diabetes GWAS (Ntotal_cases=29,469), we developed a trans-ancestry PRS (TA-PS), combining a non-HLA component incorporating over a million variants, with the HLA component of a published European PRS (GRS2x). We tested the performance of the PRS using AUROC, sensitivity and specificity in a multi-ancestry T1D case-control cohort (Ntotal= 4,657; Nnon-European=556) from Montreal, Canada. We validated our results in two independent T1D case-control cohorts (CHOP-CAG and GRACE) and two population-based cohorts (All of Us and UK Biobank). Results In our multi-ancestry Montreal-based cohort, TA-PS showed an AUROC of 0.89 which was significantly higher from the AUROC of 0.85 of GRS2x. At a 90th percentile cut-off, in African-Americans, the sensitivity of GRS2x was 0.32, compared to 0.56 in Europeans. For TA-PS, we obtained overall better sensitivities, ranging from 0.71 in Europeans to 0.77 in South Asians. TA-PS demonstrated slightly lower albeit acceptable specificity compared to that of GRS2x (> 0.83 across all ancestries). These results were validated in the four independent cohorts. 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 programs storage of TA-PS

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Keywords

Diabetes Mellitus, Type 1, diabetes type 1

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
0
Average
Average
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