A proteomic polygenic score to identify IL-18 driven inflammatory bowel disease
- 1Bristol Myers Squibb
Abstract
High levels of IL-18 have been causally implicated in IBD risk and may represent a unique mechanism driving IBD yet to be therapeutically targeted. To identify individuals predisposed to increased levels of IL-18, we implemented a polygenic approach to predict IL-18 plasma protein levels. Using a dataset with over 50,000 individuals with both genetic and plasma protein levels from Olink, we developed a 27 SNP polygenic score that predicts IL-18 levels and IBD risk. Further, we identified a threshold to classify patients as IL-18 High using a data-driven approach that optimized prediction of both IL-18 and IBD risk. We show that [~]30% of the overall IBD patient population is IL-18 High, meaning a genetic predisposition towards higher protein levels. The IL-18 PGS and corresponding threshold have the potential to identify IBD patients with IL-18-driven IBD that may respond more effectively to a therapy targeting this mechanism.
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BibTeX
@misc{turchin2026proteomic,
title = {{A proteomic polygenic score to identify IL-18 driven inflammatory bowel disease}},
author = {M. C. Turchin and N. Raghupathy and C. L. Carty and M. Morris and J. C. Maranville and E. R. Holzinger},
howpublished = {medRxiv},
year = {2026},
month = may,
doi = {10.64898/2026.05.18.26353508},
url = {https://www.medrxiv.org/content/10.64898/2026.05.18.26353508v2},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - A proteomic polygenic score to identify IL-18 driven inflammatory bowel disease
AU - M. C. Turchin
AU - N. Raghupathy
AU - C. L. Carty
AU - M. Morris
AU - J. C. Maranville
AU - E. R. Holzinger
PY - 2026
DA - 2026/05/18
PB - medRxiv
DO - 10.64898/2026.05.18.26353508
UR - https://www.medrxiv.org/content/10.64898/2026.05.18.26353508v2
AB - High levels of IL-18 have been causally implicated in IBD risk and may represent a unique mechanism driving IBD yet to be therapeutically targeted. To identify individuals predisposed to increased levels of IL-18, we implemented a polygenic approach to predict IL-18 plasma protein levels. Using a dataset with over 50,000 individuals with both genetic and plasma protein levels from Olink, we developed a 27 SNP polygenic score that predicts IL-18 levels and IBD risk. Further, we identified a threshold to classify patients as IL-18 High using a data-driven approach that optimized prediction of both IL-18 and IBD risk. We show that [~]30% of the overall IBD patient population is IL-18 High, meaning a genetic predisposition towards higher protein levels. The IL-18 PGS and corresponding threshold have the potential to identify IBD patients with IL-18-driven IBD that may respond more effectively to a therapy targeting this mechanism.
ER -