基于孟德尔随机化分析受教育程度与消化性溃疡的因果关系

王威; 邝玉慧; 刘华一; 杨阔; 李昱芃; 张涛; 张雪

doi:10.16766/j.cnki.issn.1674-4152.004549

基于孟德尔随机化分析受教育程度与消化性溃疡的因果关系

doi: 10.16766/j.cnki.issn.1674-4152.004549

王威¹,
邝玉慧¹,
刘华一^2, ,,
杨阔²,
李昱芃²,
张涛³,
张雪⁴

1.
天津中医药大学研究生院，天津 301617
2.
天津市中医药研究院附属医院脾胃科，天津 300120
3.
中国中医科学院西苑医院外一科, 北京 100091
4.
张家口市中医研究所附属医院脾胃科，河北张家口 075000

基金项目:

天津市中医药重点领域科研项目 2023004

详细信息

通讯作者:
刘华一，E-mail：15900369830@163.com

中图分类号: R573.1 R394
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出版历程
- 收稿日期: 2025-07-22
- 网络出版日期: 2026-11-10

The causal relationship between education level and peptic ulcer was analyzed based on Mendelian randomization

1.
Graduate School of Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China

摘要

摘要: 目的应用孟德尔随机化方法（MR），分析受教育程度与消化性溃疡之间可能存在的因果关系，以揭示社会经济因素与胃肠道健康之间新的生物学联系。方法基于全基因组关联研究（GWAS）汇总数据筛选单核苷酸多态性（SNPs）进行两样本MR分析，其中EA数据来源于SSCSG数据库，消化性溃疡数据来源于FinnGen数据库R10版本。采用逆方差加权法（IVW）、MR-Egger、加权中值估计法（weighted median）3种方法进行EA与消化性溃疡的因果关系判定。应用Cochran Q-test评估异质性，MR-Egger截距检验、F统计量和留一法分析进行多效性和敏感性分析，MR-PRESSO进行离群值检验。结果共筛选出604个SNP预测EA，结果IVW（OR=0.529，95% CI：0.42~0.66，P < 0.001）、MR-Egger（OR=0.451，95% CI：0.23~ 0.88，P=0.020）、weighted median（OR=0.657，95% CI：0.47~0.92，P=0.013），表明EA与消化性溃疡呈负相关关系；MR-PRESSO检验P=0.220，未发现离群SNPs；Cochran Q-test结果P=0.215，无显著异质性；MR-Egger回归截距P=0.623表明不存在水平多效性；留一法结果显示未见明显影响结果的SNPs，漏斗图显示SNP基本对称分布，结果稳健可靠。结论 EA与消化性溃疡存在负向因果关联，EA与消化性溃疡的发病风险呈负相关关系。
- 消化性溃疡 /
- 孟德尔随机化 /
- 受教育程度 /
- 全基因组关联研究
Abstract: Objective The Mendelian randomization (MR) method is applied to analyze the potential causal relationship between educational attainment and peptic ulcers, aiming to uncover novel biological links between socioeconomic factors and gastrointestinal health. Methods Single-nucleotide polymorphisms (SNPs) were screened based on the aggregated data of the genome-wide association study (GWAS). The EA data were from the SSCSG database, and the peptic ulcer data were from the R10 version of the FinnGen database. Inverse variance weighted (IVW), MR-Egger, and weighted median estimation were used to determine the causal relationship between EA and peptic ulcer. Cochran Q-test was used to evaluate heterogeneity, the MR-Egger intercept test, F-statistic, and leave-one-out analysis were used for multi-effect and sensitivity analysis, and MR-PRESSO was used for outlier test. Results A total of 604 SNPS were selected to predict EA, and the results showed that IVW (OR=0.529, 95% CI: 0.42-0.66, P < 0.001), MR-Egger (OR=0.451, 95% CI: 0.23-0.88, P=0.020), and weighted median (OR=0.657, 95% CI: 0.47-0.92, P= 0.013), indicating that EA was negatively correlated with peptic ulcer. The MR-PRESSO test detected no outlier SNPs (P= 0.220). Furthermore, Cochran's Q test indicated no significant heterogeneity (P=0.215), and the MR-Egger regression intercept test revealed no evidence of horizontal pleiotropy (P=0.623). The results of the leave-one-out analysis revealed no individual SNPs that significantly influenced the overall results, and the funnel plot displayed a generally symmetrical distribution of SNPs, suggesting that the findings are robust and reliable. Conclusion EA has a negative causal association with peptic ulcer, and EA is negatively correlated with the risk of peptic ulcer.
- Peptic ulcer /
- Mendelian randomization /
- Educational attainment /
- Genome-wide association study

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图 1 研究设计和流程图

注：LD为连锁不平衡; SNPs为单核苷酸多态性。孟德尔随机化设计的3个假设即assumption1，作为工具变量的遗传变异应该与暴露密切相关；assumption2，所使用的基因变异不应与任何混杂因素相相关；assumption3，被选择的基因变异应该只能通过暴露因素影响结果，而不是通过其他途径。

Figure 1. Study design and flow chart

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图 2 MR分析散点图

Figure 2. Scatter diagram of MR Analysis

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图 3 MR分析漏斗图

Figure 3. MR Analysis funnel diagram

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图 4 留一法敏感性分析结果(仅展示前40项SNP)

Figure 4. Results of sensitivity analysis with the leave-one method (only the top 40 SNPS are shown)

下载: 全尺寸图片幻灯片

表 1 EA与消化性溃疡的MR分析结果

Table 1. Results of MR analysis of EA and peptic ulcer

暴露因素	结局	方法	P值	OR(95% CI)
EA	消化性溃疡	IVW	1.26×10^-8	0.529(0.42~0.66)
EA	消化性溃疡	MR-Egger	0.020	0.451(0.23~0.88)
EA	消化性溃疡	weighted median	0.013	0.657(0.47~0.92)
注：OR为比值比(oddsration)；IVW为逆方差加权；MR-Egger为MR-Egger回归；weighted median为加权中位数。

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