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Evidence for genetic correlation between appendix and inflammatory bowel disease: A bidirectional Mendelian
Dan Liu1,2, Wanyue Dan1,2, Bin Yan2
1School of Medicine, Nankai University, Tianjin, China.
Plos One
|February 11, 2026
Summary
Ulcerative colitis (UC) genetically reduces the risk of appendicitis and appendectomy. However, appendicitis or appendectomy do not causally impact inflammatory bowel disease (IBD), Crohn's disease (CD), or UC risk.
Area of Science:
- Genetics
- Gastroenterology
- Epidemiology
Background:
- Observational studies suggest a link between the appendix and inflammatory bowel disease (IBD).
- Establishing causality has been challenging due to difficulties in determining temporal sequence.
- Mendelian randomization (MR) offers a method to investigate causal relationships.
Purpose of the Study:
- To investigate the causal relationship between acute appendicitis/appendectomy and IBD.
- To explore bidirectional causality using MR.
- To assess genetic correlations between appendicitis and IBD subtypes.
Main Methods:
- Two-sample bidirectional Mendelian randomization (MR) and multivariable MR.
- Linkage Disequilibrium Score Regression (LDSC) for heritability and genetic correlation.
- Genome-wide association study (GWAS) data from European ancestry.
Main Results:
- Genetically predicted ulcerative colitis (UC) was associated with reduced risk of acute appendicitis and appendectomy.
- No causal effect of acute appendicitis or appendectomy on IBD, Crohn's disease (CD), or UC was found.
- Significant negative genetic correlation between UC and acute appendicitis confirmed their inverse relationship.
Conclusions:
- Ulcerative colitis (UC) appears to causally decrease the risk of acute appendicitis and appendectomy.
- Acute appendicitis and appendectomy do not have a causal impact on IBD, UC, or CD.
- Findings suggest a protective role of UC against appendicitis, highlighting shared genetic factors.
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