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中华胃食管反流病电子杂志

中华胃食管反流病电子杂志 ›› 2025, Vol. 12 ›› Issue (02) : 62 -68. doi: 10.3877/cma.j.issn.2095-8765.2025.02.002

论著

饮食摄入习惯与胃食管反流病的因果关系：一项多变量孟德尔随机化研究
梁志强1,2,3, 侯泽辉1,2,3, 李方4, 吴晶晶4, 周太成1,2,3, 曾兵1,2,3, 李英儒1,2,3, 陈双1,2,3, 江志鹏4,†()   
  1. 1510655　广州，中山大学附属第六医院疝与腹壁外科
    2510655　广州，广东省结直肠盆底疾病研究重点实验室
    3510655　广州，广州市黄埔区中六生物医学创新研究院
    4518020　深圳市人民医院（暨南大学第二临床医学院，南方科技大学第一附属医院）普通外科，胃肠外科中心
  • 收稿日期:2024-10-31 出版日期:2025-05-15
  • 通信作者: 江志鹏
  • 基金资助:
    深圳市医学重点学科建设经费(SZXK015); 广东省和国家临床重点专科建设项目

Causal relationship between dietary intake habits and gastroesophageal reflux disease: a multivariate Mendelian Randomization Study

Zhiqiang Liang1,2,3, Zehui Hou1,2,3, Fang Li4, Jingjing Wu4, Taicheng Zhou1,2,3, Bing Zeng1,2,3, Yingru Li1,2,3, Shuang Chen1,2,3, Zhipeng Jiang4,†()   

  1. 1Department of General Surgery (Hernia and Abdominal Wall Surgery), The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, China
    2Guangdong Key Laboratory of Colorectal and Pelvic Floor Disease Research, Guangzhou 510655, China
    3Zhongliu Biomedical Innovation Research Institute, Huangpu District, Guangzhou 510655, China
    4Division of Gastrointestinal Surgery, Department of General Surgery, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China
  • Received:2024-10-31 Published:2025-05-15
  • Corresponding author: Zhipeng Jiang
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梁志强, 侯泽辉, 李方, 吴晶晶, 周太成, 曾兵, 李英儒, 陈双, 江志鹏. 饮食摄入习惯与胃食管反流病的因果关系：一项多变量孟德尔随机化研究[J/OL]. 中华胃食管反流病电子杂志, 2025, 12(02): 62-68.

Zhiqiang Liang, Zehui Hou, Fang Li, Jingjing Wu, Taicheng Zhou, Bing Zeng, Yingru Li, Shuang Chen, Zhipeng Jiang. Causal relationship between dietary intake habits and gastroesophageal reflux disease: a multivariate Mendelian Randomization Study[J/OL]. Chinese Journal of Gastroesophageal Reflux Disease(Electronic Edition), 2025, 12(02): 62-68.

目的

使用孟德尔随机化（MR）方法研究饮食摄入习惯与胃食管反流病（GERD）表型之间的因果关系。

方法

从综合流行病学单位和英国生物样本数据库纳入24种饮食摄入表型，包括谷物、肉类（禽类、牛肉、非油性鱼类、油性鱼类、猪肉、羊肉）、蔬菜摄入量（沙拉/生蔬菜摄入量和熟蔬菜）、新鲜水果、饮料（每周酒精饮料摄入量、酒精摄入频率、茶、咖啡、水、碳酸饮料和牛奶）、其他食物（奶酪、淀粉类食品消费、黑巧克力和冰淇淋）和饮食类型（食物中添加盐含量、热饮温度和低热量饮食）。从FinnGen联盟R9纳入GERD数据集，并采用MR方法分析其与GERD的因果风险。主要的MR分析方法为逆方差加权法（IVW）。计算F值统计量检验工具变量的稳定性，采用Cochran’s Q统计法进行异质性检验。同时，使用加权中位数法（WM）、MR-Egger回归和留一法评估敏感性和多效性。采用Steiger检验反向因果关系。

结果

IVW分析显示沙拉/生蔬菜摄入量（OR=0.411，95% CI：0.189~0.894；P=0.025）与降低GERD风险存在潜在的因果关联，而且IVW、WM和MR-Egger回归3种分析方法的方向一致。Steiger检验未发现结果存在反向因果关系的证据（P=2.11×10-50）。各项敏感性分析结果稳健，结果不存在异质性、多效性及反向因果关系。

结论

MR分析结果支持沙拉/生蔬菜摄入量与GERD发病风险降低有潜在因果关系。

关键词: 孟德尔随机化分析, 饮食摄入习惯, 胃食管反流病, 因果关系
Objective

To investigate the causal relationship between dietary habits and phenotypes of gastroesophageal reflux disease using Mendelian randomization.

Methods

A total of 24 dietary patterns, including cereal, meat (poultry, beef, pork, oily fish, non-oily fish, processed meat, and lamb/mutton intakes), vegetable (salad/raw vegetable and cooked vegetable intakes), fresh fruit, and beverage (alcohol intake frequency, alcoholic drinks per week, tea intake, and coffee, water, fizzy drink, and milk intakes) intakes, another food intake (cheese, starchy food, dark chocolate, and ice cream intakes), and type of diet (salt added to food, hot drink temperature, and low-calorie diet), were included from the Integrative Epidemiology Unit and UK Biobank. The GERD dataset was obtained from the FinnGen Consortium Release 9, and a Mendelian randomization approach was employed to analyze the causal association between these dietary factors and the risk of GERD. The main method of Mendelian randomization analysis was inverse variance weighting (IVW). The stability of the instrumental variables was tested by calculating the F-value statistic, and the heterogeneity was tested by Cochran’s Q statistics. In addition, weighted medians (WM). and MR-Egger regression and leave-one-out methods were used to assess sensitivity and pleiotropy. The Steiger test detects reverse causality.

Results

IVW showed that salad/raw vegetable intake (OR=0.411, 95%CI: 0.189-0.894; P=0.025), and the IVW, WM and MR-Egger regression were in the same direction. Steiger test found no evidence of reverse causality (steiger pval=2.11×10-50). The results of sensitivity analyses were robust, and there was no heterogeneity, pleiotropy, or reverse causality.

Conclusion

The results of Mendelian randomization analysis support a potential causal relationship between salad/raw vegetable intake and gastroesophageal reflux disease.

Key words: Mendelian randomization analysis, Dietary intake habits, Gastroesophageal reflux disease, Causal relationship
表1 饮食摄入与胃食管反流病的孟德尔随机化研究纳入样本数据特征
GWAS ID编号 暴露/结局 样本量 种族 机构
ieu-b-73 每周饮酒次数 335 394 欧洲人 MRC-IEU
ukb-b-5779 酒精摄入频率 462 346 欧洲人 MRC-IEU
ukb-b-8006 家禽的摄入量 461 900 欧洲人 MRC-IEU
ukb-b-2862 牛肉的摄入量 461 053 欧洲人 MRC-IEU
ukb-b-17627 非油性鱼类摄入量 460 880 欧洲人 MRC-IEU
ukb-b-2209 油性鱼类摄入量 460 443 欧洲人 MRC-IEU
ukb-b-5640 猪肉摄入量 460 162 欧洲人 MRC-IEU
ukb-b-14179 羊肉的摄入量 460 006 欧洲人 MRC-IEU
ukb-b-1489 奶酪的摄入量 451 486 欧洲人 MRC-IEU
ukb-b-8089 熟蔬菜摄入量 448 651 欧洲人 MRC-IEU
ukb-b-6066 茶摄入量 447 485 欧洲人 MRC-IEU
ukb-b-3881 新鲜水果摄入量 446 462 欧洲人 MRC-IEU
ukb-b-15926 谷类食物摄入 441 640 欧洲人 MRC-IEU
ukb-b-1996 沙拉/生蔬菜摄入量 435 435 欧洲人 MRC-IEU
ukb-b-5237 咖啡摄入量 428 860 欧洲人 MRC-IEU
ukb-b-16721 淀粉类食品消费者 64 949 欧洲人 MRC-IEU
ukb-b-8121 食物中添加盐 462 630 欧洲人 MRC-IEU
ukb-b-17189 冰淇淋的摄入量 64 949 欧洲人 MRC-IEU
ukb-b-14898 水摄入量 427 588 欧洲人 MRC-IEU
ukb-b-14203 热饮温度 457 873 欧洲人 MRC-IEU
ukb-b-2832 碳酸饮料摄入量 64 949 欧洲人 MRC-IEU
ukb-b-2966 牛奶摄入量 64 943 欧洲人 MRC-IEU
ukb-b-15768 低卡路里饮食类型 64 949 欧洲人 MRC-IEU
ukb-b-16139 黑巧克力摄入量 64 945 欧洲人 MRC-IEU
FinnGen_R9_K11 REFLUX 胃食管反流病 346 571 欧洲人 FinnGen consortium R9
图1 沙拉/生蔬菜摄入量与胃食管反流病的孟德尔随机化结果汇总森林图注：MR-IVW为逆方差加权法；WM为加权中位数法；MR-Egger为MR-Egger回归分析法；SNP为单核苷酸多态，OR为比值比
图2 沙拉/生蔬菜摄入量与胃食管反流病因果关系的孟德尔随机化（MR）散点图注：Inverse variance weighted为逆方差加权法；Weighted median为加权中位数法；MR-Egger为MR Egger回归分析；SNP为单核苷酸多态
图3 沙拉/生蔬菜摄入量与胃食管反流病因果关系的敏感性分析漏斗图注：Inverse variance weighted为逆方差加权法；Weighted median为加权中位数法；MR-Egger为MR Egger回归分析；βIV为工具变量效应估计值；1/SEIV为工具变量效应估计值的标准误的倒数
图4 沙拉/生蔬菜摄入量与胃食管反流病因果关系的留一法敏感性分析图
图5 沙拉/生蔬菜摄入量与胃食管反流病因果关系的孟德尔随机化—逆方差加权法分析的统计学功效Power值曲线图
表2 沙拉/生蔬菜摄入量与胃食管反流病因果关系的敏感性分析及Steiger分析
分析方法 统计值 数值
Cochran’s Q检验 Q值 10.96
P值 0.28
MR-Egger Intercept 截距值 0.015
P值 0.45
MR-PRESSO检验 P值 0.31
Steiger检验 因果方向 TRUE
P值 2.11×10-50
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