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Identifying environmental risk factors for inflammatory bowel diseases: a Mendelian randomization study
Robert Carreras-Torres1,2,3, Gemma Ibáñez-Sanz4,5, Mireia Obón-Santacana6,4,5
1Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Avinguda de La Granvia de L'Hospitalet, 199, 08908, Barcelona, Spain. rcarrerastorres@gmail.com.
Scientific Reports
|November 7, 2020
Summary
Mendelian randomization analysis reveals smoking increases Crohn's disease risk, while higher body fat and lower omega-3 fatty acids are linked to CD. BMI inversely affects ulcerative colitis risk.
Area of Science:
- Gastroenterology and Genetics
- Epidemiology
- Nutritional Science
Background:
- Conflicting results exist regarding environmental factors and inflammatory bowel diseases (IBD).
- Observational studies suggest lifestyle and nutrient exposures may influence IBD risk.
- A Mendelian randomization (MR) approach can help clarify causal relationships.
Purpose of the Study:
- To investigate the causal effect of lifestyle and nutrient exposures on IBD risk using MR.
- To differentiate the impact of these factors on Crohn's disease (CD) and ulcerative colitis (UC).
Main Methods:
- A two-sample MR approach utilizing summary-level genome-wide association data.
- Evaluation of genetic variants associated with smoking, obesity, physical activity, vitamins, and fatty acids.
- Analysis included 25,042 IBD cases (12,194 CD, 12,366 UC) and 34,915 controls from international consortia.
Main Results:
- Smoking showed a positive association with CD risk (OR 1.13, P=0.02) but not UC (OR 0.99, P=0.88).
- Higher body-mass index (BMI) and body fat percentage were linked to increased CD risk.
- Inverse association found between BMI and UC risk (OR 0.85, P=5x10^-5), while body fat percentage showed no significant association with UC.
- Higher omega-3 fatty acid levels were inversely associated with CD risk (OR 0.67, P=2x10^-6).
Conclusions:
- MR results support smoking as a risk factor for CD, not UC.
- Higher body fat proportion appears to increase CD risk.
- Elevated omega-3 fatty acid levels may offer protection against CD.
- BMI has differential effects on CD and UC risk.
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