Analysis of the Intrinsic Mechanism of "Cardio-Gastric Correlation" from the Genetic Association Between Depression and Functional Dyspepsia

Author：XU Yichuan1, FENG Yiyi2, NI Jing1, LIN Jiang1, LU Lu1

Unit：1.Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; 2.Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou Zhejiang 310003, China

Quote：引用：许异川，冯依伊，倪晶，林江，卢璐.从抑郁和功能性消化不良的遗传关联分析“心胃相关”内在机制[J].中医药导报,2025,31(9):199-205.

DOI：10.13862/j.cn43-1446/r.2025.09.033

PDF： Download PDF

Abstract：

Objective: To investigate the causal relationships between mood disorders and functional dyspepsia (FD) at the genetic level and the underlying mechanism based on "cardio-gastric correlation". Methods: Mendelian randomization (MR) analysis was conducted using summary data from genome-wide association studies. The inverse variance weighting, weighted median, and MR-Egger regression were used for analysis, and sensitivity analysis was performed to verify the robustness of the results. Bayesian colocalization analysis was used to identify potential common genetic loci between depression and FD. Enrichment analysis was performed on depression-related SNP-mapped genes to clarify possible pathogenic mechanisms, and MR analysis was used to evaluate the effect of these genes on FD. Results: The results from inverse variance weighted method showed that depression increased the risk of FD (OR=1.501, 95% CI:1.104-2.040, P=0.009). The reverse analysis did not reveal any causal association. Enrichment analysis suggested that depression-related genes were mainly enriched in synaptic function and calcium signaling pathways. Further MR analysis indicated that increased expression of RSRC1 was associated with an increased risk of FD (OR=1.13, 95% CI:1.07-1.20, P＜0.001). Conclusion: This study found that depression increases the risk of FD, and the mechanism may be related to abnormalities in synaptic function and calcium signaling pathways, with RSRC1 being a key gene in the causal association.

Key words：functional dyspepsia; anxiety; depression; traditional Chinese medicine theory; Mendelian randomization

摘要：目的：基于“心胃相关”理论探讨情绪障碍和功能性消化不良（FD）在遗传水平上的因果关联以及潜在机制。方法：采用全基因组关联分析的汇总数据进行孟德尔随机化（MR）分析。使用逆方差加权法、加权中位数法、MR-Egger回归进行分析并进行敏感性分析以验证结果的稳健性；采用贝叶斯共定位分析确定抑郁和FD之间可能的共同遗传位点；对抑郁相关SNP的映射基因进行富集分析以阐明可能的致病机制；采用MR分析评估这些基因对FD的作用。结果：逆方差加权法的结果显示抑郁会增加FD的发病风险（OR=1.501，95%CI:1.104-2.040，P=0.009）；反向分析未发现任何的因果关联；富集分析提示抑郁的相关基因主要富集于突触功能和钙信号通路；进一步的MR分析提示RSRC1的表达升高与FD的发病风险升高相关（OR=1.13，95%CI:1.07-1.20，P＜0.001）。结论：抑郁增加了FD的发病风险，其机制可能与突触功能和钙信号通路相关，且RSRC1是其遗传关联中的关键基因。

关键词：功能性消化不良；焦虑；抑郁；中医理论；孟德尔随机化

Release time：2026-01-08

click-through rate：162