Page 118 - 《南京医科大学学报》2026年第1期

南京医科大学学报（自然科学版） 第46卷第1期
· 112 · Journal of Nanjing Medical University（Natural Sciences） 2026年1月

·临床研究·

抑郁与胃食管反流病相关表型的遗传关联性分析

邵燕婷，徐亭亭 *

上海中医药大学附属岳阳中西医结合医院消化科，上海 200437

［摘 要］ 目的：研究表明抑郁与胃食管反流病（gastroesophageal reflux disease，GERD）存在显著相关性，但两者间的因果关系
及关联方向尚不明确，本研究旨在从遗传层面探索抑郁与GERD及其亚型的双向因果推断与疾病潜在机制。方法：基于抑郁、
GERD、反流性食管炎（reflux esophagitis，RE）与非糜烂型胃食管反流病（non⁃erosive reflux disease，NERD）的全基因组关联研究
（genome⁃wide association study，GWAS）汇总数据，利用孟德尔随机化（Mendelian randomization，MR）探索抑郁与 GERD、RE、
NERD的独立因果关系。整合GWAS、表达数量性状位点（expression quantitative trait loci，eQTL）等多组学数据，通过基于汇总
数据的孟德尔随机化（summary⁃data⁃based Mendelian randomization，SMR）、遗传关联的功能映射和注释（functional mapping and
annotation，FUMA）等方法探索抑郁与GERD及其亚型的潜在致病基因，并通过富集分析评估抑郁影响GERD及其亚型的潜在
机制。结果：抑郁会增加GERD与NERD的发病风险，但不会增加RE的发病风险。GERD、RE、NERD不会增加抑郁的发病风
险。通过 SMR、FUMA 分析确定抑郁的潜在易感基因为 RPL31P12，GERD 的潜在易感基因为 NCSTN，NERD 潜在易感基因为
SPATS2L。抑郁与GERD共同基因位点主要富集在T细胞受体信号通路、DNA结合转录因子活性、RNA聚合酶Ⅱ转录调控区
域序列特异性DNA结合等方面。抑郁与NERD共同基因位点主要富集在核小体组装、蛋白质及复合物亚基组装、T细胞受体
信号通路等方面。结论：抑郁会增加GERD、NERD发病风险，其潜在机制可能借助脑⁃肠轴，通过神经免疫通路，DNA、RNA转
录与调控，蛋白质代谢等发挥作用。
［关键词］ 抑郁；胃食管反流病；遗传关联；孟德尔随机化
［中图分类号］ R571；R749.4 ［文献标志码］ A ［文章编号］ 1007⁃4368（2026）01⁃112⁃11
doi：10.7655/NYDXBNSN250350

Genetic correlation analysis between depression and gastroesophageal reflux disease
related phenotypes
SHAO Yanting，XU Tingting *
Department of Gastroenterology，Yueyang Hospital of Integrated Chinese and Western Medicine Affiliated to Shanghai
University of Traditional Chinese Medicine，Shanghai 200437，China

［Abstract］ Objective：Studies have shown that there is a significant correlation between depression and gastroesophageal reflux
disease（GERD），but the causal relationship between the two and the direction of correlation are not clear. This study aims to explore
the bidirectional causal inference between depression and GERD as well as its subtypes and the underlying mechanism of the disease
from the genetic level. Methods：Based on the aggregated data of the genome⁃wide association study（GWAS）of depression，GERD，

reflux esophagitis（RE）and non⁃erosive gastroesophageal reflux disease（NERD），Mendelian randomization was used to explore the
independent causal relationship between depression and GERD，RE and NERD. Multiple omics data，such as GWAS and expression
quantitative trait loci（eQTL），were integrated to explore the potential pathogenic genes of depression，GERD and its subtypes by
summary ⁃ data ⁃ based Mendelian randomization（SMR）and functional mapping and annotation（FUMA）methods. The potential
mechanism of depression affecting GERD and its subtypes was evaluated by enrichment analysis. Results：Depression increased the
risk of GERD and NERD，but not RE. GERD，RE，and NERD did not increase the risk of depression. Through SMR and FUMA
analysis，the potential susceptibility gene for depression was identified as RPL31P12，and the potential susceptibility gene for GERD
was identified as NCSTN. The NERD potential susceptibility gene was SPATS2L. Depression and GERD gene common loci were

［基金项目］ 国家自然科学基金（82405248）；上海中医药大学科技发展项目（23KFL115）
通信作者（Corresponding author），E⁃mail：yy2758@shutcm.edu.cn（ORCID：0000⁃0002⁃8353⁃9196）
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