Depression and 24 gastrointestinal diseases: a Mendelian randomization study.
Depression and 24 gastrointestinal diseases: a Mendelian randomization study.
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DOI：
10.1038/s41398-023-02459-6
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发表时间：
2023-05-04
影响因子：
6.8
通讯作者：
Larsson, Susanna C. C.
中科院分区：
文献类型：
--
作者：
Ruan, Xixian;Chen, Jie;Sun, Yuhao;Zhang, Yao;Zhao, Jianhui;Wang, Xiaoyan;Li, Xue;Yuan, Shuai;Larsson, Susanna C. C.
抑郁症与胃肠道疾病之间的因果关系尚不确定。我们进行孟德尔随机化（MR）分析，系统地探讨抑郁症与24种胃肠道疾病的关系。在全基因组显著性水平上与抑郁症相关的独立遗传变异被选为工具变量。从英国生物库研究、FinnGen研究和大型财团中获得了与24种胃肠道疾病的遗传关联。多变量MR分析，探讨身体质量指数，吸烟和2型糖尿病的中介作用。经过多重检验校正后，抑郁症的遗传易感性与肠易激综合征、非酒精性脂肪肝、酒精性肝病、胃食管反流、慢性胰腺炎、十二指肠溃疡、慢性胃炎、胃溃疡、憩室病、胆石症、急性胰腺炎和溃疡性结肠炎的风险增加相关。对于抑郁症的遗传易感性对非酒精性脂肪肝的因果影响，很大一部分是由体重指数介导的。吸烟的遗传易感性介导抑郁症对急性胰腺炎的一半影响。这项MR研究表明，抑郁症可能在许多胃肠道疾病中发挥因果作用。
The causality of the association between depression and gastrointestinal diseases is undetermined. We conducted Mendelian randomization (MR) analyses to systematically explore the associations of depression with 24 gastrointestinal diseases. Independent genetic variants associated with depression at the genome-wide significance level were selected as instrumental variables. Genetic associations with 24 gastrointestinal diseases were obtained from the UK Biobank study, the FinnGen study, and large consortia. Multivariable MR analysis was conducted to explore the mediation effects of body mass index, cigarette smoking, and type 2 diabetes. After multiple-testing corrections, genetic liability to depression was associated with an increased risk of irritable bowel syndrome, non-alcohol fatty liver disease, alcoholic liver disease, gastroesophageal reflux, chronic pancreatitis, duodenal ulcer, chronic gastritis, gastric ulcer, diverticular disease, cholelithiasis, acute pancreatitis, and ulcerative colitis. For the causal effect of genetic liability to depression on non-alcoholic fatty liver disease, a substantial proportion was mediated by body mass index. Genetic predisposition to smoking initiation mediated half of effect of depression on acute pancreatitis. This MR study suggests that depression may play a causal role in many gastrointestinal diseases.
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