Modifiable factors for irritable bowel syndrome: evidence from Mendelian randomisation approach

Area of Science:

• Genetics
• Gastroenterology
• Epidemiology

Background:

• Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with incompletely understood modifiable risk factors.
• Previous research has not comprehensively documented factors influencing IBS, necessitating systematic investigation.
• Understanding these factors is crucial for developing effective prevention and management strategies.

Purpose of the Study:

• To systematically investigate modifiable factors and coexisting disorders associated with IBS.
• To account for unobserved confounders and the impact of comorbid conditions.
• To leverage genetic correlation and Mendelian randomization (MR) analyses for robust causal inference.

Main Methods:

• Integrated genetic correlation and Mendelian randomization (MR) analyses.
• Employed multi-response MR (MR²) to examine bidirectional associations.
• Utilized summary-level genome-wide association data for IBS, modifiable factors, and gastrointestinal/psychiatric disorders.

Main Results:

• Identified significant genetic correlations between IBS and numerous factors, including multisite chronic pain, GERD, well-being, life satisfaction, positive affect, neuroticism, and depression.
• MR analyses confirmed strong causal links between IBS and multisite chronic pain (OR=2.20), GERD (OR=1.31), and depression (OR=1.50), while revealing protective associations with well-being (OR=0.17) and life satisfaction (OR=0.31).
• Suggestive associations were noted for smoking, alcohol, education, intelligence, childhood maltreatment, frailty, diverticular disease, and schizophrenia; multisite chronic pain demonstrated robust links with IBS and coexisting disorders.

Conclusions:

• This study provides comprehensive genetic evidence linking IBS to various modifiable factors and coexisting disorders.
• Multisite chronic pain emerges as a significant factor with strong causal associations with IBS and related conditions.
• Targeting multisite chronic pain may represent a promising strategy for the simultaneous prevention of IBS and its common comorbidities.