Environmental variables and genome-environment interactions predicting IBD diagnosis in large UK cohort

Abstract

A combination of genetic susceptibility and environmental exposure is thought to cause inflammatory bowel disease (IBD), but the non-genetic component remains poorly characterized. We therefore undertook a search for environmental variables and gene-environment interactions associated with future IBD diagnosis in a large UK cohort. Using self-report and electronic health records, we identified 1946 Crohn’s disease (CD) and 3715 ulcerative colitis (UC) patients after quality control in the UK Biobank. Based on prior literature and biological plausibility , we tested 38 candidate environmental variables for association with CD, UC, and overall IBD using Cox proportional hazard regressions. We also tested whether these variables interacted with polygenic risk in predicting disease, following up significant (FDR < 0.05) results with tests for SNP-environment associations. We performed robustness analyses on all significant results. As in previous reports, appendectomy protected against UC, smoking (both current and previous) elevated risk for CD, current smoking protected against UC, and previous smoking imparted a risk for UC. Childhood antibiotic use associated with IBD, as did sun exposure during the winter. Socioeconomic deprivation was conferred a risk for IBD, CD, and UC. We uncovered negative interactions between polygenic risk and previous oral contraceptive use for IBD and UC. Polygenic risk also interacted negatively with previous smoking in predicting UC. There were no individually significant SNP-environment interactions. Thus, for a limited set of environmental variables, there was strong evidence of association with IBD diagnosis in the UK Biobank, and interaction with polygenic risk was minimal.

A Specialized Epithelial Cell Type Regulating Mucosal Immunity and Driving Human Crohn’s Disease

“…CD can affect any portion of the gastrointestinal tract with inflammation that can span across all layers of the gut, while UC is localized to the colon and rectum and confined to the mucosa. IBD is believed to be driven from the complex interplay between environmental factors and genetic susceptibilities, resulting in dysregulated immune responses to environmental triggers and the breakdown of the epithelial barrier and intestinal homeostasis (Torres et al, 2017; Van Heel et al, 2001; Yang and Jostins-Dean, 2022). Genome-wide association studies have revealed more than 200 IBD-susceptiblility genes, which are involved in microbial sensing, antigen presentation, autophagy, T-cell signaling, and other immune-related pathways (de Lange et al, 2017; Jostins et al, 2012; Liu et al, 2015; Momozawa et al, 2018).…”

Helminth Lessons in Inflammatory Bowel Diseases (IBD)

“…IBD is a chronic inflammatory disorder of the gastrointestinal tract that is caused by genetic susceptibility and environmental factors [ 35 , 36 , 37 ]. It is generally categorized into two subtypes, Crohn’s disease (CD) and ulcerative colitis (UC), based on clinical pathological features.…”

Integration and implementation of precision medicine in the multifaceted inflammatory bowel disease

“…Patients with increased genetic risk for IBD but healthy lifestyles had a lower risk of developing IBD than those with increased genetic risk and unhealthy lifestyles (HR: 2.23 vs 4.40)[ 25 ]. Yang and Jostins-Dean[ 26 ] published data using the information of IBD patients from a United Kingdom biobank. They analyzed 24 dietary exposures, perinatal childhood exposures, and lifestyle factors in individuals.…”

“…They showed that multiple factors interacted, causing polygenic risk in predicting IBD occurrence. Factors such as appendectomy, smoking, childhood antibiotic use, exposure to the sun in winter, socioeconomic factors, and oral contraceptive use played a role in IBD pathogenesis[ 26 ]. Ryan et al [ 27 ] found that inflamed and non-inflamed colonic mucosa in IBD patients had different microbiota composition and epigenetic profiles.…”