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Abstract：
Mendelian randomization method is a powerful tool in epidemiological research. The core idea is to use genetic variation as a tool to assess the causal relationship between risk factors and specific diseases. Confounding factors are important interference factors for causal inference in epidemiological studies, and genetic variation in Mendelian randomization studies follows the principle of random distribution of alleles to offspring, which is similar to randomized controlled trials. Mendel \'s randomization method can effectively avoid the confounding factors, reverse causality in observational studies and the representativeness and feasibility of randomized controlled trials. Previous observational studies have reported a relationship between negative emotions and upper gastrointestinal disease. However, whether this relationship is causal remains unclear. We aimed to evaluate the causal relationship between negative emotions and upper gastrointestinal diseases using two-sample Mendelian randomization (MR). Three sets of genetic instruments from the database were obtained for analysis, including 12 anxiety-related single nucleotide polymorphisms (SNPs), 46 depression-related SNPs, and 58 nervous-related SNPs. SNPs were filtered using the Phenoscanner website, and the inverse variance weighted method, weighted median method, MR-Egger regression, MR pleiotropy residual sum, and outlier test were used for analysis. In inverse variance weighted analysis, anxiety and depression had an effect on gastroduodenal ulcer (p = 2.849×10-3, β = 4.908, 95% CI = 1.684-8.132; and p = 6.457×10-4, β = 1.767, 95% CI = 0.752-2.782, respectively). Additionally, depression had an effect on diseases of the esophagus, stomach, and duodenum (p = 3.498×10-5, β = 0.926, 95% CI = 0.487-1.364). Cochran\'s Q-derived p-values were 0.457, 0.603, and 0.643, and MR-Egger intercept-derived p-values were 0.697, 0.294, and 0.362, respectively. Here, we show that anxiety and depression have a causal relationship with gastroduodenal ulcers, and depression has a causal relationship with diseases of the esophagus, stomach, and duodenum.
摘要：
孟德尔随机化方法是流行病学研究的有力工具。核心思想是将遗传变异作为评估风险因素与特定疾病之间因果关系的工具。混杂因素是流行病学研究中因果推断的重要干扰因素,孟德尔随机化研究中的遗传变异遵循等位基因随机分布到后代的原则，这与随机对照试验相似。孟德尔的随机化方法可以有效地避免混杂因素,观察性研究中的反向因果关系以及随机对照试验的代表性和可行性。先前的观察性研究报道了负面情绪与上消化道疾病之间的关系。然而,这种关系是否是因果关系尚不清楚.我们旨在使用双样本孟德尔随机化（MR）评估负面情绪与上消化道疾病之间的因果关系。从数据库中获得了三套遗传仪器进行分析,包括12个焦虑相关的单核苷酸多态性（SNPs），46个抑郁相关的SNP，和58个神经相关的SNP。SNP使用Phenoscanner网站过滤，和逆方差加权法，加权中位数法，MR-Egger回归，MR多效性残差总和，并采用离群检验进行分析。在逆方差加权分析中，焦虑和抑郁对胃十二指肠溃疡有影响（p=2.849×10-3，β=4.908，95％CI=1.684-8.132；p=6.457×10-4，β=1.767，95％CI=0.752-2.782）。此外,抑郁症对食道疾病有影响，胃,十二指肠（p=3.498×10-5，β=0.926，95%CI=0.487-1.364）。Cochran的Q推导的p值分别为0.457、0.603和0.643，MR-Egger截距推导的p值分别为0.697、0.294和0.362。这里,我们发现焦虑和抑郁与胃十二指肠溃疡有因果关系，抑郁症与食道疾病有因果关系，胃,和十二指肠。
