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Article History

Received: 9 October 2024

Accepted: 21 February 2025

First Online: 10 May 2025

Acknowledgements

: Parts of the content of this manuscript were communicated as an oral presentation at the ADA 81st Scientific Meeting in June 2021 and at the 6th Annual Diabetes Prevention Symposium in November 2023.

: The datasets generated during and/or analysed in the current study are available from the corresponding author upon reasonable request. Interactive figures can be found online at .

: The R code and the predictive model parameters that belong to the Pareto front are available at . Code to generate the HLA interaction part of the GRS2 is freely available online ().

: Open access funding provided by University of Geneva. This work was funded by NIH grants R01 DK121843-01 (to MJR, AKS, LY, SO-G, PAG, SSR, JK and RAO) and grant 3-SRA-2019-827-S-B from Breakthrough T1D (formerly known as JDRF) (to LAF and RAO). TMT is supported by National Institute of Diabetes and Digestive and Kidney Diseases grant K23 DK136931. The Type 1 Diabetes TrialNet Study Group is a clinical trials network that is currently funded by the NIH through the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, and The Eunice Kennedy Shriver National Institute of Child Health and Human Development, through the cooperative agreements U01 DK061010, U01 DK061034, U01 DK061042, U01 DK061058, U01 DK085461, U01 DK085465, U01 DK085466, U01 DK085476, U01 DK085499, U01 DK085509, U01 DK103180, U01 DK103153, U01 DK103266, U01 DK103282, U01 DK106984, U01 DK106994, U01 DK107013, U01 DK107014, UC4 DK106993, UC4DK117009, and by Breakthrough T1D (formerly known as JDRF). The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or Breakthrough T1D.

: RAO has received consulting fees from Janssen R & D, and previously held a UK MRC Confidence in Concept grant to develop a 10 SNP type 1 diabetes GRS biochip with Randox R & D, and received research funding from Randox R & D. MJR is a member of the Editorial Board of Diabetologia. The remaining authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.

: LAF, ELT, RAO and MJR contributed to the study design, as well as data analysis and interpretation, and wrote the first draft of the manuscript. AKS, RBM, JK, HMP and LY contributed to the study design and data interpretation. PAG, SO-G, TMT and SSR contributed to data interpretation. All authors revised, edited and approved the final version of the manuscript. AKS, HMP, LY, PAG, TMT, JK and MJR were members of the Type 1 Diabetes TrialNet Study Group at the time of the study. LAF, RAO and MJR are the guarantors of this article and take full responsibility for the work as a whole, including the study design, access to data and the decision to submit and publish the manuscript.