Type 1 diabetes (T1D) polygenic risk scores (PRS) are effective tools for discriminating T1D from other diabetes types and predicting T1D risk, with applications in screening and intervention trials. A previously published T1D Genetic Risk Score 2 (GRS2) is widely adopted, but challenges in standardization and accessibility have hindered broader clinical and research utility. To address this, we introduce GRS2x, a standardized and cross-compatible method for accurate T1D PRS calculation, demonstrating genotyping and reference panel independent performance across diverse datasets. GRS2x as a unified approach facilitates accessible and portable measurement of T1D polygenic risk.

ALGs spouse is employed by Genentech and holds stock options in Roche. ML, RAO and MNW have funding from Randox to study Translation of Autoimmune Genetic Scores. The University of Exeter have a licensing and royalty agreement with Randox relating to a 10 SNP T1D GRS. No other potential conflicts of interest relevant to this article were reported.

A.M.L. is funded by a PhD studentship from Randox Laboratories Ltd. A.J.D. is funded by NIDDK K23DK140643. RAO is funded by NIDDK (R01DK121843, R01DK124395), Breakthrough T1D (4-SRA-2023-1375-M-B, 3-SRA-2022-1241-S-B, 2-SRA-2022-1261-S-B, 2-SRA-2022-1258-M-B, 2-SRA-2024-1620-S-B), The Leona M. and Harry B. Helmsley Charitable Trust (2016PG-T1D049, 2018PG-T1D049, 2103-05059, and G-2404-06858), and Randox Ltd. H.I.O. is funded by NIDDK T32DK007217 and Stanford Maternal and Childrens Health Research Institute. A.K.M. is supported by the FNIH with funding from AMP CMD RFP 2 and NHGRI U01HG011723. J.M.M. is supported by ADA grant #11-22-ICTSPM-16 and by NHGRI U01HG011723 and NIDDK R01DK137993 and U01 DK140757, AMP CMD award from RFP 6 from the FNIH, and a Medical University of Bialystok (MUB) grant from the Ministry of Science and Higher Education (Poland). M.A.R. is supported by NHGRI R01HG010140 and NIMH R01MH124244. M.S.U is funded by Doris Duke Clinical Scientist Development Award 2022063, NHGRI U01HG011723, and NIDDK (U54DK118612, UM1DK126185, U01DK140757). A.L.G. is funded by NIDDK (UM1-1DK126185, P30 DK116074). S.A.S. is funded by the Larry L. Hillblom Foundation (2024-D-017-FEL).

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This research utilized data from the UK Biobank resource carried out under UK Biobank application number 9072. UK Biobank protocols were approved by the National Research Ethics Service Committee. Deidentified Clinical and genetic data for this study were analyzed through the All of Us Research Program (https://allofus.nih.gov/) Researcher Workbench platform. Access to the dataset was granted under Data Use and Registration Agreement (DURA) and all analyses complied with the program ethical and data usage policies. All necessary approvals were obtained from the Type 1 Diabetes Genetics Consortium under a data use agreement.

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