Evidence for genetic correlation between appendix and inflammatory bowel disease: A bidirectional Mendelian randomization study

Dan Liu, Wanyue Dan, Bin Yan, Lihua Peng and Fei Pan

PLOS ONE, 2026, vol. 21, issue 2, 1-12

Abstract: Background: Observational studies highlighted a link between the appendix and inflammatory bowel disease (IBD), but proving causality has been difficult due to the lack of a clear temporal sequence. Methods: This research used a two-sample bidirectional univariable Mendelian randomization (MR), multivariable MR and linkage disequilibrium score regression (LDSC) analyses to explore the relationship between acute appendicitis, appendectomy, and IBD. Eligible instrumental variables were screened from previous genome-wide association studies (GWAS) of European ancestry for analysis. The inverse variance-weighted method was used for the primary analysis. Sensitivity analyses were used to detect and correct pleiotropy. LDSC analysis determined SNP-based heritability (h2) for acute appendicitis, IBD, Crohn’s disease (CD), and ulcerative colitis (UC). Following that, cross-trait LDSC analysis assessed genetic correlations (rg) between these traits using GWAS summary data. Results: Genetically predicted UC was significantly associated with a lower risk of acute appendicitis (OR = 0.933, 95% CI 0.911–0.957, p

Date: 2026
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0342541

DOI: 10.1371/journal.pone.0342541

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