Mendelian randomization analysis reveals causal relationship between tonsillectomy and irritable bowel syndrome

Area of Science:

• Genetics and Epidemiology
• Gastroenterology
• Otolaryngology

Background:

• Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with complex etiology.
• The potential causal link between tonsillectomy and IBS remains incompletely understood.
• Mendelian randomization offers a robust approach to investigate causal relationships using genetic variants.

Purpose of the Study:

• To evaluate the potential causal effect of tonsillectomy on the risk of developing irritable bowel syndrome (IBS).
• To leverage genetic data and advanced statistical methods for robust causal inference.

Main Methods:

• Two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data.
• Identification of single nucleotide polymorphisms (SNPs) as instrumental variables for tonsillectomy.
• Application of inverse-variance weighted (IVW) as the primary method, with MR-Egger, weighted median (WM), weighted mode (WME), and simple mode as sensitivity analyses.
• Assessment of heterogeneity using Cochran's Q tests and horizontal pleiotropy using the MR-Egger intercept.

Main Results:

• Genetically predicted tonsillectomy showed a positive association with an increased risk of IBS (OR = 1.682, P = 0.006).
• Significant heterogeneity was detected among SNPs (Cochran's Q test, P = 3.13 × 10⁻⁵).
• No significant horizontal pleiotropy was detected (MR-Egger intercept, P = 0.789), and sensitivity analyses supported result stability.

Conclusions:

• Genetic evidence suggests a positive causal relationship between tonsillectomy and an increased risk of IBS.
• Findings indicate a need for enhanced preventive measures for IBS in individuals who have undergone tonsillectomy.