ArticlePloS one2026
Evidence for genetic correlation between appendix and inflammatory bowel disease: A bidirectional Mendelian randomization study.
Article in PloS one, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundObservational 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.
methodsThis 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.
resultsGenetically predicted UC was significantly associated with a lower risk of acute appendicitis (OR = 0.933, 95% CI 0.911-0.957, p < 0.001) and appendectomy (OR = 0.954, 95% CI 0.932-0.976, p < 0.001). Conversely, no causal effect was observed from acute appendicitis or appendectomy on IBD, UC, or CD. While a suggestive association was noted for CD with appendectomy in univariable analysis, it did not remain significant after multivariable adjustment for the influence of UC. A significant negative genetic correlation further supported the inverse relationship between UC and acute appendicitis (rg = -0.205, p = 0.005).
conclusionsIn conclusion, genetically predicted UC was causally associated with a decreased risk of acute appendicitis and appendectomy, but neither acute appendicitis nor appendectomy has a causal impact on the risk of IBD, UC, or CD. These findings suggest that ulcerative colitis (UC) may confer a protective effect against the development of acute appendicitis, offering valuable insights into the shared genetic architecture and potential biological mechanisms underlying these conditions.
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