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

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.

Genetically predicted circulating B vitamins in relation to digestive system cancers

“… 38 Furthermore, a recent MR study revealed a positive association between genetically predicted high serum vitamin B12 concentrations and risk of inflammatory bowel disease, especially Crohn’s disease. 39 This may be of relevance as patients diagnosed with inflammatory bowel disease have an increased risk of developing colorectal cancer. 40 …”

Mendelian Randomization Rules Out Causation Between Inflammatory Bowel Disease and Non-Alcoholic Fatty Liver Disease

“…Thanks to the rapid development of genome-wide association study (GWAS) and accumulation of publicly available GWAS summary statistics, MR design based on two-sample setting is becoming more flexible and accessible. Several MR studies have identified causal risk factors of IBD, such as body fat percentage ( Carreras-Torres et al, 2020 ) and ankylosing spondylitis ( Cui et al, 2020 ). Also, a MR study clarified the causal relationship between NAFLD, type 2 diabetes (T2D) and obesity ( Liu et al, 2020 ).…”

A systematic review on application of deep learning in digestive system image processing

“…In recent years, studies have found interactions and pathological similarities between IBD and metabolic disorders, including metabolic tissue disorders, inadequate immune response, and inflammatory response [ 53 ]. Patients with non-alcoholic fatty liver diseases (NAFLD) or a high body fat percentage are at higher risk for IBD [ 54 , 55 ]. Combined with the patient’s clinical symptoms, MRI fat quantification could be applied to CAD of IBD and diabetes in future.…”