Chen Dongze, Zhang Yali, Huang Tao, Jia Jinzhu
Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.
Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100083, China.
Psychol Med. 2023 Nov;53(15):7309-7321. doi: 10.1017/S0033291723000867. Epub 2023 May 15.
Major depressive disorder (MDD) is clinically documented to co-occur with multiple gastrointestinal disorders (GID), but the potential causal relationship between them remains unclear. We aimed to evaluate the potential causal relationship of MDD with 4 GID [gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), peptic ulcer disease (PUD), and non-alcoholic fatty liver disease (NAFLD)] using a two-sample Mendelian randomization (MR) design.
We obtained genome-wide association data for MDD from a meta-analysis ( = 480 359), and for GID from the UK Biobank ( ranges: 332 601-486 601) and FinnGen ( ranges: 187 028-218 792) among individuals of European ancestry. Our primary method was inverse-variance weighted (IVW) MR, with a series of sensitivity analyses to test the hypothesis of MR. Individual study estimates were pooled using fixed-effect meta-analysis.
Meta-analyses IVW MR found evidence that genetically predicted MDD may increase the risk of GERD, IBS, PUD and NAFLD. Additionally, reverse MR found evidence of genetically predicted GERD or IBS may increase the risk of MDD.
Genetically predicted MDD may increase the risk of GERD, IBS, PUD and NAFLD. Genetically predicted GERD or IBS may increase the risk of MDD. The findings may help elucidate the mechanisms underlying the co-morbidity of MDD and GID. Focusing on GID symptoms in patients with MDD and emotional problems in patients with GID is important for the clinical management.
临床记录显示，重度抑郁症（MDD）常与多种胃肠道疾病（GID）同时发生，但其潜在因果关系尚不清楚。我们旨在采用两样本孟德尔随机化（MR）设计，评估MDD与4种GID[胃食管反流病（GERD）、肠易激综合征（IBS）、消化性溃疡病（PUD）和非酒精性脂肪性肝病（NAFLD）]之间的潜在因果关系。
我们从一项荟萃分析中获得了MDD的全基因组关联数据（n = 480359），以及来自英国生物银行（样本量范围：332601 - 486601）和芬兰基因库（样本量范围：187028 - 218792）的欧洲血统个体的GID数据。我们的主要方法是逆方差加权（IVW）MR，并进行了一系列敏感性分析以检验MR假设。使用固定效应荟萃分析汇总个体研究估计值。
荟萃分析IVW MR发现证据表明，基因预测的MDD可能会增加GERD、IBS、PUD和NAFLD的风险。此外，反向MR发现证据表明，基因预测的GERD或IBS可能会增加MDD的风险。
基因预测的MDD可能会增加GERD、IBS、PUD和NAFLD的风险。基因预测的GERD或IBS可能会增加MDD的风险。这些发现可能有助于阐明MDD和GID共病的潜在机制。关注MDD患者的GID症状以及GID患者的情绪问题对临床管理很重要。
