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. 2024 Mar 26;15:2568. doi: 10.1038/s41467-023-44512-4

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — Development and validation of the polygenic risk scores (PRSs) for ulcerative colitis and Crohn’s disease was conducted in cancer-free individuals using UK Biobank and BioVU. LDPred2 method was used to tune the parameters for the PRS for ulcerative colitis and Crohn’s disease (PRS_UC, PRS_CD) in 70% of the UK Biobank, using the summary statistics from the largest genome-wide association study of UC and CD. The PRSs were then tested in the remaining 30% of the UK Biobank and validated in BioVU. In the next step, the role of PRS_UC and PRS_CD on all-grade and severe immune checkpoint inhibitor-mediated colitis (IMC) was evaluated in a cohort of 1316 non-small cell lung cancer patients who received at least one dose of immune checkpoint inhibitor therapy. Furthermore, replication was conducted using 873 pan-cancer patients treated with immune checkpoint inhibitors obtained from BioVU. Finally, associations of all-grade and severe IMC along with PRS_UC and PRS_CD on progression-free survival (PFS) and overall survival (OS) were assessed. Figure created with BioRender.com.