Objective:

To summarize current evidence of gene-environment interactions (GXE) in inflammatory bowel disease (IBD) and highlight their significance.

Key Findings:

• 39 eligible studies identified, with 17 reporting statistically significant interactions, indicating a substantial body of evidence.
• NOD2-smoking interaction was the most frequently investigated, showing a variant-specific effect at rs2066847 for Crohn’s disease, which may inform targeted interventions.
• Gene-smoking interactions identified in several IBD risk genes and detoxification genes, suggesting a complex interplay that warrants further exploration.
• Gene-diet interactions observed with various nutritional measures and specific genes, highlighting the potential for dietary modifications in IBD management.

Interpretation:

The risk of IBD conferred by environmental factors varies among individuals with specific genetic variants, indicating the need for personalized lifestyle and dietary recommendations that could be tailored based on genetic profiles.

Limitations:

• Low consistency in results across studies regarding environmental factors, with examples of methodological differences such as sample size and study design.
• Methodological differences and unstandardized definitions of environmental factors may affect findings, complicating the interpretation of results.

Conclusion:

Further research, including genome-wide environment interaction studies and genotype-based clinical trials, is necessary to understand the heritability influenced by environmental exposures and to construct personalized recommendations of lifestyle/dietary modification based on an individual genetic background, particularly focusing on high-risk populations.