New College, Oxford, UK.
Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Headington, OX3 7FY, Oxfordshire, UK.
Sci Rep. 2022 Jun 28;12(1):10890. doi: 10.1038/s41598-022-13222-0.
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.
遗传易感性和环境暴露的结合被认为是导致炎症性肠病（IBD）的原因，但非遗传成分仍未得到充分描述。因此，我们在一个大型英国队列中进行了一项研究，以寻找与未来 IBD 诊断相关的环境变量和基因-环境相互作用。我们使用自我报告和电子健康记录，在英国生物库中进行质量控制后，确定了 1946 例克罗恩病（CD）和 3715 例溃疡性结肠炎（UC）患者。基于先前的文献和生物学合理性，我们使用 Cox 比例风险回归检验了 38 个候选环境变量与 CD、UC 和总体 IBD 的关联。我们还测试了这些变量是否与多基因风险相互作用，以预测疾病，对有意义的（FDR < 0.05）结果进行 SNP-环境关联的测试。我们对所有显著结果进行了稳健性分析。与之前的报告一样，阑尾切除术可预防 UC，吸烟（当前和以前）增加 CD 的风险，当前吸烟可预防 UC，以前吸烟会增加 UC 的风险。儿童时期使用抗生素与 IBD 有关，冬季暴露于阳光下也与 IBD 有关。社会经济贫困与 IBD、CD 和 UC 相关。我们发现多基因风险与以前口服避孕药的使用对 IBD 和 UC 有负性相互作用。多基因风险与以前吸烟对 UC 的预测也有负性相互作用。没有单独的 SNP-环境相互作用具有统计学意义。因此，对于一组有限的环境变量，在英国生物库中发现与 IBD 诊断有很强的关联，并且与多基因风险的相互作用最小。
