抑郁与炎症性肠病：一项双向二样本孟德尔随机化研究。

Depression and Inflammatory Bowel Disease: A Bidirectional Two-sample Mendelian Randomization Study.

机构信息

Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.

Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.

出版信息

J Crohns Colitis. 2022 May 10;16(4):633-642. doi: 10.1093/ecco-jcc/jjab191.

DOI:10.1093/ecco-jcc/jjab191

PMID:34739073

Abstract

BACKGROUND AND AIMS

Observational studies have suggested a bidirectional association between depression and inflammatory bowel disease [IBD], including Crohn's disease [CD] and ulcerative colitis [UC]. However, it remains unclear whether the observed associations are causal due to the difficulties of determining sequential temporality. We investigated the association between depression and IBD by using bidirectional two-sample Mendelian randomization [MR].

METHODS

Independent genetic variants for depression and IBD were selected as instruments from published genome-wide association studies [GWAS] among individuals of predominantly European ancestry. Summary statistics for instrument-outcome associations were retrieved from three separate databases for both depression [Psychiatric Genomics Consortium, FinnGen and UK Biobank] and IBD [the largest GWAS meta-analysis, FinnGen and UK Biobank], respectively. MR analyses included the inverse-variance-weighted method, weighted-median estimator, MR-Egger regression, and sensitivity analyses of Steiger filtering and MR PRESSO. From either direction, analyses were performed per outcome database and were subsequently meta-analysed using a fixed-effect model.

RESULTS

Genetically predicted depression [per log-odds ratio increase] was associated with a higher risk of IBD; odds ratios [95% confidence interval] for IBD, CD and UC were 1.20 [1.05, 1.36], 1.29 [1.07, 1.56] and 1.22 [1.01, 1.47] in a combined sample size of 693 183 [36 507 IBD cases], 212 172 [13 714 CD cases] and 219 686 [15 691 UC cases] individuals, respectively. In contrast, no association was observed between genetically influenced IBD and depression in 534 635 individuals [71 466 depression cases].

CONCLUSIONS

Our findings corroborated a causal association of depression on IBD, which may impact the clinical decision on the management of depression in patients with IBD. Though our results did not support a causal effect of IBD on depression, further investigations are needed to clarify the effect of IBD activity on depression [with different symptomology].

摘要

背景和目的

观察性研究表明，抑郁和炎症性肠病[IBD]之间存在双向关联，包括克罗恩病[CD]和溃疡性结肠炎[UC]。然而，由于难以确定先后顺序的时间性，观察到的关联是否具有因果关系尚不清楚。我们通过双向两样本孟德尔随机化[MR]研究来探讨抑郁和 IBD 之间的关联。

方法

从主要为欧洲血统个体的已发表全基因组关联研究[GWAS]中选择用于抑郁和 IBD 的独立遗传变异作为工具。从三个独立的数据库中检索用于抑郁[精神基因组学联合会、芬兰遗传和英国生物银行]和 IBD[最大的 GWAS 荟萃分析、芬兰遗传和英国生物银行]的工具-结果关联的汇总统计数据。MR 分析包括逆方差加权法、加权中位数估计、MR-Egger 回归以及 Steiger 过滤和 MR PRESSO 的敏感性分析。从任一方向，根据结果数据库进行分析，然后使用固定效应模型进行荟萃分析。

结果

遗传预测的抑郁[每对数优势比增加]与 IBD 的风险增加相关；IBD、CD 和 UC 的比值比[95%置信区间]在 693 183 例[36 507 例 IBD 病例]、212 172 例[13 714 例 CD 病例]和 219 686 例[15 691 例 UC 病例]个体的综合样本中分别为 1.20 [1.05, 1.36]、1.29 [1.07, 1.56]和 1.22 [1.01, 1.47]。相比之下，在 534 635 例个体[71 466 例抑郁病例]中，没有观察到遗传影响的 IBD 和抑郁之间的关联。