Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Nov 6;10(1):19273.
doi: 10.1038/s41598-020-76361-2.

Identifying environmental risk factors for inflammatory bowel diseases: a Mendelian randomization study

Robert Carreras-Torres  1   2   3 , Gemma Ibáñez-Sanz  4   5 , Mireia Obón-Santacana  6   4   5 , Eric J Duell  6   4 , Victor Moreno  6   4   5   7
Affiliations

Identifying environmental risk factors for inflammatory bowel diseases: a Mendelian randomization study

Robert Carreras-Torres et al. Sci Rep. .

Abstract

Several studies have examined environmental factors and inflammatory bowel diseases (IBD) using traditional approaches; however, provided results are still conflicting. Our aim was to determine whether lifestyle and nutrient exposures, related to IBD in observational meta-analyses, influence IBD risk using a Mendelian randomization (MR) approach. A two-sample MR approach was applied on summary-level genome-wide association results. Genetic variants strongly associated with measures of tobacco smoking, obesity and fat distribution, physical activity, and blood levels of vitamins and fatty acids were evaluated on genetic data from international IBD consortia including a total of 25,042 IBD cases (12,194 cases of Crohn's disease (CD) and 12,366 cases of ulcerative colitis (UC)) and 34,915 controls. Our results indicated that, among lifestyle exposures, being a smoker was positively associated with CD (OR 1.13, P = 0.02), but it was not associated with UC risk (OR 0.99, P = 0.88). Body-mass index (BMI) and body fat percentage were positively associated with CD (OR 1.11, P = 0.02, per standard deviation (SD) of 4.6 kg/m2; and OR 1.50, P = 3 × 10-10, per SD of 6.6%; respectively); while for UC, BMI was inversely associated (OR 0.85, P = 5 × 10-5; per SD) and body fat percentage showed a OR of 1.11 (P = 0.11; per SD). Additionally, among nutrient exposures, omega-3 fatty acids levels were inversely associated with CD (OR 0.67, P = 2 × 10-6). Our MR results did not support a protective effect for being a smoker on UC risk; however, they are compatible with a risk effect for higher body fat proportion and a protective role for higher levels of omega-3 fatty acids on CD etiology.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Mendelian randomization as an analogous approach to a classical randomized control trial (RCT).
Figure 2
Figure 2
Forest plot of IBD risk for increment in lifestyle exposures. OR per standard deviation increase were estimated using likelihood-based MR approach. 95% CI 95% confidence interval; P P value. Pdisease het P value of heterogeneity between Crohn’s disease (CD) and ulcerative colitis (UC).
Figure 3
Figure 3
Scatter plots depicting summary statistics for genetic association and likelihood-based MR results of smoking status on CD (a), and smoking status on UC (b).
Figure 4
Figure 4
Scatter plots depicting summary statistics for genetic association and likelihood-based MR results of body-mass index on UC (a), and body fat percentage on CD (b).
Figure 5
Figure 5
Forest plot of IBD risk for increment in nutrient exposures. OR per standard deviation increase were estimated using likelihood-based MR approach. 95% CI: 95% Confidence Interval; P: P value. Pdisease het: P value of heterogeneity between Crohn’s disease (CD) and ulcerative colitis (UC).
Figure 6
Figure 6
Scatter plots depicting summary statistics for genetic association and likelihood-based MR results of vitamin D on IBD (a), and omega-3 fatty acids on CD (b).
See this image and copyright information in PMC

References

    1. Abraham C, Cho JH. Inflammatory bowel disease. N. Engl. J. Med. 2009;361:2066–2078. doi: 10.1056/NEJMra0804647. - DOI - PMC - PubMed
    1. Gomollón F, et al. 3rd European evidence-based consensus on the diagnosis and management of Crohn’s disease 2016: Part 1: Diagnosis and medical management. J. Crohn’s Colitis. 2017;11:3–25. doi: 10.1093/ecco-jcc/jjw168. - DOI - PubMed
    1. Magro F, et al. Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: definitions, diagnosis, extra-intestinal manifestations, pregnancy, cancer surveillance, surgery, and Ileo-anal pouch disorders. J. Crohn’s Colitis. 2017;11:649–670. doi: 10.1093/ecco-jcc/jjx008. - DOI - PubMed
    1. Ng SC, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2017;390:2769–2778. doi: 10.1016/S0140-6736(17)32448-0. - DOI - PubMed
    1. Halfvarson J, et al. Dynamics of the human gut microbiome in inflammatory bowel disease. Nat. Microbiol. 2017;2:1–7. doi: 10.1038/nmicrobiol.2017.4. - DOI - PMC - PubMed

Publication types

MeSH terms