PDF(Pubmed)
Abstract：
Mendelian randomization (MR) was used to evaluate the bidirectional causal relationship between inflammatory bowel disease (IBD) and interleukins (ILs), chemokines.
Genetic instruments and summary data of five ILs and six chemokines were obtained from a genome-wide association study database, and instrumental variables related to IBD were obtained from the FinnGen Consortium. Inverse variance weighting (IVW) was used as the main MR analysis method, and several other MR methods including MR-Egger and weighted median were used to confirm the reliability of the results. Sensitivity analyses such as heterogeneity and pleiotropy were also performed.
The IVW method provided evidence to support that genetically predicted IL-16, IL-18, and CXCL10 significantly positively correlated with IBD, while IL-12p70 and CCL23 significantly negatively correlated with IBD. IL-16 and IL-18 had a suggestive association with an increased risk of ulcerative colitis (UC), and CXCL10 had a suggestive association with an increased risk of Crohn\'s disease (CD). However, there was no evidence to support that IBD and two main subtypes (UC and CD) are associated with changes in the levels of ILs and chemokines. The results of the sensitivity analyses were robust and no evidence of heterogeneity and horizontal pleiotropy was observed.
The present study showed that some ILs and chemokines affect IBD, but IBD and its main subtypes (UC and CD) have no effect on the level changes of ILs and chemokines.
Genetic instruments and summary data of five ILs and six chemokines were obtained from a genome-wide association study database, and instrumental variables related to IBD were obtained from the FinnGen Consortium. Inverse variance weighting (IVW) was used as the main MR analysis method, and several other MR methods including MR-Egger and weighted median were used to confirm the reliability of the results. Sensitivity analyses such as heterogeneity and pleiotropy were also performed.
The IVW method provided evidence to support that genetically predicted IL-16, IL-18, and CXCL10 significantly positively correlated with IBD, while IL-12p70 and CCL23 significantly negatively correlated with IBD. IL-16 and IL-18 had a suggestive association with an increased risk of ulcerative colitis (UC), and CXCL10 had a suggestive association with an increased risk of Crohn\'s disease (CD). However, there was no evidence to support that IBD and two main subtypes (UC and CD) are associated with changes in the levels of ILs and chemokines. The results of the sensitivity analyses were robust and no evidence of heterogeneity and horizontal pleiotropy was observed.
The present study showed that some ILs and chemokines affect IBD, but IBD and its main subtypes (UC and CD) have no effect on the level changes of ILs and chemokines.
摘要：
■孟德尔随机化（MR）用于评估炎症性肠病（IBD）与白细胞介素（IL）之间的双向因果关系，趋化因子.
■从全基因组关联研究数据库中获得了五种IL和六种趋化因子的遗传仪器和汇总数据，与IBD相关的工具变量是从FinnGen联盟获得的。采用方差逆加权(IVW)作为主要的MR分析方法，以及包括MR-Egger和加权中位数在内的其他几种MR方法用于确认结果的可靠性。还进行了敏感性分析，如异质性和多效性。
■IVW方法提供了证据支持基因预测的IL-16，IL-18和CXCL10与IBD显着正相关，IL-12p70和CCL23与IBD呈显著负相关。IL-16和IL-18与溃疡性结肠炎（UC）的风险增加有暗示性关联，CXCL10与克罗恩病（CD）的风险增加有暗示性关联。然而,没有证据支持IBD和两种主要亚型(UC和CD)与IL和趋化因子水平的变化相关.敏感性分析的结果是稳健的，没有观察到异质性和水平多效性的证据。
■本研究表明，一些IL和趋化因子影响IBD，但IBD及其主要亚型（UC和CD）对IL和趋化因子的水平变化没有影响。
■从全基因组关联研究数据库中获得了五种IL和六种趋化因子的遗传仪器和汇总数据，与IBD相关的工具变量是从FinnGen联盟获得的。采用方差逆加权(IVW)作为主要的MR分析方法，以及包括MR-Egger和加权中位数在内的其他几种MR方法用于确认结果的可靠性。还进行了敏感性分析，如异质性和多效性。
■IVW方法提供了证据支持基因预测的IL-16，IL-18和CXCL10与IBD显着正相关，IL-12p70和CCL23与IBD呈显著负相关。IL-16和IL-18与溃疡性结肠炎（UC）的风险增加有暗示性关联，CXCL10与克罗恩病（CD）的风险增加有暗示性关联。然而,没有证据支持IBD和两种主要亚型(UC和CD)与IL和趋化因子水平的变化相关.敏感性分析的结果是稳健的，没有观察到异质性和水平多效性的证据。
■本研究表明，一些IL和趋化因子影响IBD，但IBD及其主要亚型（UC和CD）对IL和趋化因子的水平变化没有影响。
