Unraveling the link between inflammatory bowel disease and perianal abscess: insights from bidirectional and multivariable Mendelian randomization study
Jul 29, 2025BMC gastroenterology
Genetic links between inflammatory bowel disease and perianal abscess risk
is associated with a 20% increased risk of developing .
IBD, including Crohn's disease (CD) and ulcerative colitis (UC), has been identified as a risk factor for perianal abscess.
For IBD, the observed odds ratio for perianal abscess risk was 1.20 (95%CI = 1.12-1.31), indicating a significant association.
Subtypes of IBD showed specific associations: CD had an odds ratio of 1.15 (95%CI = 1.06-1.24) and UC had an odds ratio of 1.11 (95%CI = 1.01-1.21).
These associations were consistent in independent cohorts, reinforcing the findings with odds ratios of 1.17 for IBD, 1.12 for CD, and 1.13 for UC.
Bidirectional analysis did not show significant associations between perianal abscess liability and IBD progression.
MVMR analyses confirmed a direct causal relationship, indicating that IBD influences the risk of developing perianal abscess.
AI simplified
BACKGROUND: Emerging epidemiological studies have identified associations between (PA) and (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), though the pathophysiological mechanisms underlying their comorbidity remain incompletely understood. To elucidate potential causal relationships between these clinical entities, we conducted a comprehensive investigation employing bidirectional two-sample (MR) analysis complemented by multivariable Mendelian randomization (MVMR) methodology. This analytical approach enables systematic evaluation of causal directionality while accounting for potential confounding factors inherent in observational studies.
METHODS: To establish valid instrumental variables, independent single nucleotide polymorphisms (SNPs) were selected from genome-wide association study (GWAS) summary statistics of European ancestry populations. Data for IBD were sourced from the IEU OpenGWAS repository, while PA datasets were obtained from FinnGen consortium and UK Biobank resources. Our bidirectional MR framework incorporated five complementary analytical methods: inverse variance weighted (IVW), weighted median, MR-Egger regression, weighted mode, and simple mode estimators. Methodological robustness was ensured through comprehensive sensitivity analyses: horizontal pleiotropy was evaluated via MR-Egger intercept testing, heterogeneity quantified using Cochran's Q statistic, and outlier detection implemented through MR-PRESSO (Mendelian Randomization Pleiotropy Residual Sum and Outlier) with supplementary leave-one-out validation to assess individual SNP influence on causal estimates.
RESULTS: Genetic liability analyses using IVW estimation revealed IBD) and its principal subtypes as risk factors for PA. In the discovery cohort, IBD conferred a 20% increased PA risk (OR = 1.20, 95%CI = 1.12-1.31, p = 5.68 Γ 10β»β΅), with subtype-specific effects for CD (OR = 1.15, 95%CI = 1.06-1.24, p = 0.0004) and UC (OR = 1.11, 95%CI = 1.01-1.21, p = 0.027). These associations replicated consistently in the independent cohort (IBD: OR = 1.17, 95%CI = 1.09-1.27, p = 3.92 Γ 10β»β΅; CD: OR = 1.12, 95%CI = 1.04-1.21, p = 0.002; UC: OR = 1.13, 95%CI = 1.03-1.24, p = 0.009). Conversely, IVW-based bidirectional analysis demonstrated non-significant associations between PA liability and IBD progression across both cohorts (all p > 0.05). Confounder-adjusted MVMR analyses confirmed direct causal effects of IBD (encompassing CD and UC) on PA risk after accounting for pleiotropy. In exploration cohorts, ulcerative ileocolitis in CD exhibited nominal association with elevated perianal disease risk (OR = 1.18, 95%CI = 1.01-1.38, p = 0.04) in hypothesis-generating analyses.
CONCLUSIONS: Our analyses demonstrated significant associations between PA and both principal IBD subtypes (UC and CD), underscoring the necessity for mechanistic investigations into shared pathophysiology within the IBD spectrum.
Key numbers
1.20
Increase in PA risk
Odds ratio for increasing PA risk in the discovery cohort
1.15
Increase in PA risk for CD
Odds ratio for CD increasing PA risk
1.11
Increase in PA risk for UC
Odds ratio for UC increasing PA risk
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