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.
J Crohns Colitis. 2022 May 10;16(4):633-642. doi: 10.1093/ecco-jcc/jjab191.
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].
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.
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].
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].
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。
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。
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。
我们的发现证实了抑郁对 IBD 的因果关系，这可能会影响 IBD 患者抑郁管理的临床决策。尽管我们的结果不支持 IBD 对抑郁的因果影响，但需要进一步研究来阐明 IBD 活动对抑郁的影响[具有不同的症状学]。
