| Title: | Associations of polygenic risk scores with intestinal surgery, gastrointestinal cancer, and all-cause mortality in 5,021 individuals with inflammatory bowel disease |
| Journal: | Scientific Reports |
| Published: | 22 Aug 2026 |
| DOI: | https://doi.org/10.1038/s41598-026-68136-y |
| URL: | http://dx.doi.org/10.1038/s41598-026-68136-y |
Publication 20927
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Abstract
Polygenic risk scores (PRS) predict inflammatory bowel disease (IBD) susceptibility, but their associations with outcomes after diagnosis are uncertain. We studied 5,021 UK Biobank participants with Crohn's disease (CD; n = 1,427) or ulcerative colitis (UC; n = 3,594). Cox-model estimates for disease-specific standardized PRS were pooled across 20 imputed datasets. A clinically extended model included disease duration, log-transformed C-reactive protein, previous intestinal surgery, and baseline aminosalicylate, corticosteroid, and immunomodulator use in addition to demographic and lifestyle covariates. Benjamini-Hochberg false-discovery rate (FDR) correction covered six disease-outcome tests. In CD, each 1-SD higher PRS was associated with intestinal surgery (HR = 1.61, 95% CI 1.31-1.99; P < 0.001; FDR < 0.001); the high versus low tertile estimate was HR = 2.70 (95% CI 1.58-4.62; FDR = 0.004). CD PRS was not associated with gastrointestinal cancer or mortality. In UC, associations with surgery (P = 0.482), gastrointestinal cancer (HR = 1.21, 95% CI 0.99-1.48; P = 0.065; FDR = 0.130), and mortality (HR = 1.10, 95% CI 1.00-1.22; P = 0.058; FDR = 0.130) were nonsignificant. The CD surgery association persisted among participants without previous surgery (HR = 1.62, 95% CI 1.29-2.04; P < 0.001). These genetic epidemiology associations do not establish incremental prediction or clinical utility and require external validation.</p>
8 Authors
- Yifan Yuan
- Yue Feng
- Dongguang Wang
- Jiatong Xie
- Hongjin An
- Han Zhou
- Wei Shi
- Huatian Gan
1 Application
| Application ID | Title |
|---|---|
| 630220 | Multi-omics and Multi-dimensional Data Analysis: Investigating the Impact of Lifestyle, Biological Aging, Metabolic Changes, and Protein Expression on Gastrointestinal Diseases - An Integrative Study |
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