Unveiling the Intricate Causal Nexus Between 91 Circulating Inflammatory Proteins and Perianal Abscess Through a Comprehensive Bidirectional Two-Sample Mendelian Randomization Analysis.

BACKGROUND

The link between circulating inflammatory proteins and perianal abscess remains uncertain. This study utilized the Mendelian randomization approach to examine the potential causality of 91 circulating inflammatory proteins in relation to perianal abscess (PA) and assessed the bidirectionality of these causal effects.

METHODS

We conducted analyses using Genome-wide Association Studies (GWAS) summary statistics for 91 circulating inflammatory proteins, sourced from 11 cohorts with a combined total of 14,824 participants. Genetic associations for PA were taken from the FinnGen Consortium R9 data, consisting of 2595 PA cases and 301,931 control individuals. Two-sample Mendelian randomization (MR) analysis was utilized to investigate the causal links between these inflammatory proteins and PA. To validate the reliability of our MR findings, sensitivity analyses were carried out. Furthermore, reverse Mendelian randomization was employed to assess whether there is evidence for a reciprocal causal effect.

RESULTS

Employing the inverse-variance weighted (IVW) approach, our findings identified 7 circulating inflammatory proteins with a potential causal link to PA. Notably, increased levels of interleukin-18 receptor 1 (OR = 1.10, 95% CI 1.01-1.19,  = 0.039), interleukin-33 (OR = 1.31, 95% CI 1.10-1.56,  = 0.002), interleukin-7 (OR = 1.32, 95% CI 1.06-1.64,  = 0.014), and tumor necrosis factor ligand superfamily member 12 (OR = 1.16, 95% CI 1.01-1.32,  = 0.032) showed associations with increased risk for PA. Conversely, higher levels of T-cell surface glycoprotein CD6 isoform (OR = 0.81, 95% CI 0.68-0.98,  = 0.026), interleukin-2 (OR = 0.80, 95% CI 0.66-0.97,  = 0.026), and programmed cell death 1 ligand 1 (OR = 0.84, 95% CI 0.70-1.00,  = 0.047) appeared to have protective effects against this condition. Additionally, our analysis has not found any evidence to suggest a reverse causal relationship between PA and the 7 specific inflammatory factors studied.

CONCLUSIONS

Our Mendelian randomization analysis identifies a probable causal association involving 91 circulating inflammatory proteins and the risk of PA development.