Department of Gastroenterology, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China.
Department of Dermatology, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China.
Front Immunol. 2023 Jul 3;14:1203707. doi: 10.3389/fimmu.2023.1203707. eCollection 2023.
Previous observational or retrospective studies have suggested an association between inflammatory bowel disease (IBD) and herpes virus infections. Using Mendelian randomization (MR) approach, our objective was to determine whether there was a causal association between IBD and herpes virus infections.
In genome-wide association study (GWAS) datasets of the International Inflammatory Bowel Disease Genetics Consortium, we obtained genetic instrumental variables for three phenotypes from 34,652 participants (12,882 IBD cases and 21,770 controls), 27,432 participants [6,968 ulcerative colitis (UC) cases and 20,464 controls], and 20,883 participants [5,956 Crohn's disease (CD) cases and 14,927 controls], respectively. Summary statistics for herpes virus infections (chickenpox, herpes zoster, and mononucleosis) were obtained from the FinnGen database. MR results were expressed as odds ratio (OR) with 95% confidence interval (CI).
Our study found no evidence of a causal effect of genetically predicted IBD on herpes virus infections [ value for inverse variance weighting (IVW): 0.063 to 0.652]. For the subtypes of IBD, UC had a suggestive association with mononucleosis ( value for IVW: 0.023). It appeared that CD was also weakly associated with mononucleosis ( value for IVW: 0.058; value for Weighted median: 0.036). In addition, we found a suggestive causality for CD on chickenpox ( value for IVW: 0.038). Neither UC ( value for IVW: 0.574) nor CD ( value for IVW: 0.168) has a causal effect on herpes zoster. The results of the bidirectional MR analysis did not indicate that herpes virus infections were associated with IBD, UC or CD ( value for IVW: 0.239 to 0.888).
This study showed a suggestive causality for both CD-chickenpox and UC-mononucleosis, despite no associations reaching a statistical significance value after corrections for multiple testing. There was no evidence of a causal association between IBD and its two subtypes on herpes zoster.
先前的观察性或回顾性研究表明，炎症性肠病（IBD）与疱疹病毒感染之间存在关联。本研究采用孟德尔随机化（MR）方法，旨在确定 IBD 与疱疹病毒感染之间是否存在因果关系。
我们从国际炎症性肠病遗传学联合会的全基因组关联研究（GWAS）数据集获得了来自 34652 名参与者（12882 例 IBD 病例和 21770 名对照）、27432 名参与者（6968 例溃疡性结肠炎（UC）病例和 20464 名对照）和 20883 名参与者（5956 例克罗恩病（CD）病例和 14927 名对照）的三种表型的遗传工具变量。疱疹病毒感染（水痘、带状疱疹和单核细胞增多症）的汇总统计数据来自芬兰基因（FinnGen）数据库。MR 结果表示为比值比（OR）及其 95%置信区间（CI）。
本研究未发现遗传预测的 IBD 对疱疹病毒感染有因果影响（逆方差加权（IVW）值：0.063 至 0.652）。对于 IBD 的亚型，UC 与单核细胞增多症呈显著关联（IVW 值：0.023）。CD 似乎也与单核细胞增多症呈弱相关（IVW 值：0.058；加权中位数：0.036）。此外，我们发现 CD 与水痘之间存在因果关系的提示（IVW 值：0.038）。UC（IVW 值：0.574）和 CD（IVW 值：0.168）均与带状疱疹无因果关系。双向 MR 分析的结果表明，疱疹病毒感染与 IBD、UC 或 CD 之间无关联（IVW 值：0.239 至 0.888）。
尽管经过多次检验校正后，没有关联达到统计学显著性水平，但本研究仍显示 CD-水痘和 UC-单核细胞增多症之间存在因果关系的提示。IBD 及其两个亚型与疱疹病毒感染之间无因果关系。
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