据报道，炎症性肠病（IBD）与恶性肿瘤，包括淋巴瘤，的风险增加有关。很多大型观察性研究致力于探究IBD和恶性淋巴瘤之间的因果关系。然而，目前尚无共识，是否存在IBD和恶性淋巴瘤之间的因果关系。IBD和淋巴瘤全基因组关联研究（GWAS）的汇总数据集获取自OPEN GWAS网站。在IBD GWAS中，以P < 5 × 10-8和连锁不平衡（LD）的r2 = 0.001为标准，选择单核苷酸多态性（SNP）作为遗传工具变异体（IV）。鉴定具有r2 > 0.8的代理SNP。排除回文SNP和异常SNP。敏感性评估采用了Cochran's Q检验、Mendelian randomization（MR）-Egger截距检验和one-out分析。MR分析结果证明了IBD对弥漫性大B细胞淋巴瘤（DLBCL）的因果关系。IBD患者患DLBCL的风险增加了28.6% [概率比（OR）IVW = 1.286，95%置信区间（CI）1.066-1.552，P = 0.009]。亚组分析结果显示，克罗恩病（ORIVW = 1.218，95%CI 1.030-1.441，P = 0.021），而非溃疡性结肠炎（ORIVW = 1.206，95%CI 0.984-1.478，P = 0.072），对DLBCL具有因果作用。MR研究中未观察到横向和定向的遗传多功能性。以上MR研究得出结论，IBD本身对DLBCL，特别是克罗恩病具有直接的因果性作用。需要进一步研究以阐明此直接因果关系的机制。 Copyright © 2023 Lu, Chen, Tao, Xu, Li, Wang and Yu.

It has been reported that inflammatory bowel disease (IBD) is associated with an increased risk of malignancies, including lymphoma. A number of large observational studies have been devoted to exploring the causal link between IBD and malignant lymphoma. However, no consensus exists on whether there is a causal relationship between IBD and malignant lymphoma.The summary dataset of the IBD and lymphoma genome-wide association studies (GWAS) was obtained from the OPEN GWAS website. Single-nucleotide polymorphisms (SNPs) were selected as genetic instrumental variants (IVs) for fulling P < 5 × 10-8 and linkage disequilibrium (LD) of r2 = 0.001 in the IBD GWAS. The proxy SNPs with LD of r2 > 0.8 were identified. Palindromic SNPs and outlier SNPs were excluded. The assessments of sensitivity employed the Cochran's Q test, Mendelian randomization (MR)-Egger intercept test, and leave-one-out analysis.The MR analysis results proved the causality of IBD on diffuse large B-cell lymphoma (DLBCL). The risk of developing DLBCL is increased by 28.6% in patients with IBD [odds ratio (OR)IVW = 1.286, 95% confidence interval (CI) 1.066-1.552, P = 0.009]. The results of the subgroup analysis showed that Crohn's disease (ORIVW = 1.218, 95% CI 1.030-1.441, P = 0.021) rather than ulcerative colitis (ORIVW = 1.206, 95% CI 0.984-1.478, P = 0.072) had a causal effect on DLBCL. No horizontal and directional pleiotropy was observed in the MR studies.The above MR study concluded that IBD itself is causally responsible for DLBCL, especially Crohn's disease. Further investigations are needed to elucidate the mechanism underlying this direct causal link.Copyright © 2023 Lu, Chen, Tao, Xu, Li, Wang and Yu.