Association between psychiatric disorders and irritable bowel syndrome: A bidirectional Mendelian randomization study

Area of Science:

• Psychiatry and Gastroenterology
• Genetic Epidemiology
• Complex Disease Etiology

Background:

• Irritable bowel syndrome (IBS) is frequently comorbid with psychiatric disorders, but causal relationships remain debated.
• Distinguishing causal, concomitant, or accidental associations is crucial for understanding disease mechanisms.

Purpose of the Study:

• To employ Mendelian randomization (MR) analysis to ascertain the causal effects of psychiatric disorders on IBS.
• To investigate potential bidirectional causal relationships between IBS and psychiatric conditions.

Main Methods:

• Utilized genome-wide association study (GWAS) summary data from large cohorts, including the Psychiatric Genomics Consortium (PGC).
• Applied three MR methods: inverse-variance weighting (IVW), weighted median (WM), and MR-Egger regression.
• Assessed heterogeneity and horizontal pleiotropy using Cochran's Q statistic and MR-Egger intercept.

Main Results:

• Significant causal effect of schizophrenia on IBS identified via MR-IVW.
• Evidence suggests major depressive disorder (MDD) and schizophrenia have causal effects on IBS.
• Bidirectional causality observed, with IBS also demonstrating causal effects on MDD.
• SNP heritability varied significantly across disorders, with high heritability for bipolar disorder and schizophrenia, and lower for MDD, anxiety, PTSD, and IBS.

Conclusions:

• Established causal links between major depressive disorder and schizophrenia with irritable bowel syndrome.
• Confirmed a bidirectional relationship, indicating IBS can also causally influence major depressive disorder.
• Provides robust evidence for a causal component in the association between specific psychiatric disorders and IBS.