Mendelian randomisation analysis for intestinal disease: achievement and future

Area of Science:

• Gastroenterology and Digestive Diseases
• Genetic Epidemiology
• Causal Inference Methods

Background:

• Intestinal diseases represent a significant global health burden, necessitating accurate identification of risk factors and complications.
• Traditional observational studies face limitations in establishing causality due to confounding factors and reverse causation.
• Mendelian randomization (MR) offers a robust approach to overcome these limitations in causal inference.

Purpose of the Study:

• To introduce the Mendelian randomization (MR) methodology for studying intestinal diseases.
• To summarize existing MR research on risk factors and causal relationships in intestinal diseases.
• To outline future research directions, including multiomics and diverse ancestral populations.

Main Methods:

• Review of Mendelian randomization (MR) studies applied to intestinal disease.
• Summary of findings related to lifestyle behaviors, nutrients, obesity markers, and inflammatory biomarkers.
• Discussion of multiomics MR and triangulation with other epidemiological methods.

Main Results:

• MR studies have validated conventional risk factors such as physical activity, smoking, alcohol consumption, selenium, BMI, waist-to-hip ratio, and inflammatory biomarkers.
• Multiomics MR studies are emerging as a key area for understanding pathogenesis and identifying drug targets.
• Current MR research predominantly focuses on European populations, highlighting the need for replication in other ancestries.

Conclusions:

• Mendelian randomization is a powerful tool for establishing causal links between risk factors and intestinal diseases.
• Future research should leverage multiomics data and ensure diverse ancestral representation for generalizable findings.
• Triangulation of MR with other epidemiological methods provides a validated framework for robust causal inference.