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Abstract：
BACKGROUND: Previous observational studies have shown that the prevalence of gastroesophageal reflux disease (GERD) and Barrett\'s esophagus (BE) is associated with socioeconomic status. However, due to the methodological limitations of traditional observational studies, it is challenging to definitively establish causality.
OBJECTIVE: To explore the causal relationship between the prevalence of these conditions and socioeconomic status using Mendelian randomization (MR).
METHODS: We initially screened single nucleotide polymorphisms (SNPs) to serve as proxies for eight socioeconomic status phenotypes for univariate MR analysis. The inverse variance weighted (IVW) method was used as the primary analytical method to estimate the causal relationship between the eight socioeconomic status phenotypes and the risk of GERD and BE. We then collected combinations of SNPs as composite proxies for the eight socioeconomic phenotypes to perform multivariate MR (MVMR) analyses based on the IVW MVMR model. Furthermore, a two-step MR mediation analysis was used to examine the potential mediation of the associations by body mass index, major depressive disorder (MDD), smoking, alcohol consumption, and sleep duration.
RESULTS: The study identified three socioeconomic statuses that had a significant impact on GERD. These included household income [odds ratio (OR): 0.46; 95% confidence interval (95%CI): 0.31-0.70], education attainment (OR: 0.23; 95%CI: 0.18-0.29), and the Townsend Deprivation Index at recruitment (OR: 1.57; 95%CI: 1.04-2.37). These factors were found to independently and predominantly influence the genetic causal effect of GERD. Furthermore, the mediating effect of educational attainment on GERD was found to be mediated by MDD (proportion mediated: 10.83%). Similarly, the effect of educational attainment on BE was mediated by MDD (proportion mediated: 10.58%) and the number of cigarettes smoked per day (proportion mediated: 3.50%). Additionally, the mediating effect of household income on GERD was observed to be mediated by sleep duration (proportion mediated: 9.75%).
CONCLUSIONS: This MR study shed light on the link between socioeconomic status and GERD or BE, providing insights for the prevention of esophageal cancer and precancerous lesions.
OBJECTIVE: To explore the causal relationship between the prevalence of these conditions and socioeconomic status using Mendelian randomization (MR).
METHODS: We initially screened single nucleotide polymorphisms (SNPs) to serve as proxies for eight socioeconomic status phenotypes for univariate MR analysis. The inverse variance weighted (IVW) method was used as the primary analytical method to estimate the causal relationship between the eight socioeconomic status phenotypes and the risk of GERD and BE. We then collected combinations of SNPs as composite proxies for the eight socioeconomic phenotypes to perform multivariate MR (MVMR) analyses based on the IVW MVMR model. Furthermore, a two-step MR mediation analysis was used to examine the potential mediation of the associations by body mass index, major depressive disorder (MDD), smoking, alcohol consumption, and sleep duration.
RESULTS: The study identified three socioeconomic statuses that had a significant impact on GERD. These included household income [odds ratio (OR): 0.46; 95% confidence interval (95%CI): 0.31-0.70], education attainment (OR: 0.23; 95%CI: 0.18-0.29), and the Townsend Deprivation Index at recruitment (OR: 1.57; 95%CI: 1.04-2.37). These factors were found to independently and predominantly influence the genetic causal effect of GERD. Furthermore, the mediating effect of educational attainment on GERD was found to be mediated by MDD (proportion mediated: 10.83%). Similarly, the effect of educational attainment on BE was mediated by MDD (proportion mediated: 10.58%) and the number of cigarettes smoked per day (proportion mediated: 3.50%). Additionally, the mediating effect of household income on GERD was observed to be mediated by sleep duration (proportion mediated: 9.75%).
CONCLUSIONS: This MR study shed light on the link between socioeconomic status and GERD or BE, providing insights for the prevention of esophageal cancer and precancerous lesions.
摘要：
背景：先前的观察性研究表明，胃食管反流病（GERD）和Barrett食管（BE）的患病率与社会经济状况有关。然而,由于传统观察性研究的方法局限性，确定因果关系是具有挑战性的。
目的：使用孟德尔随机化（MR）探索这些疾病的患病率与社会经济状况之间的因果关系。
方法：我们最初筛选了单核苷酸多态性（SNPs），作为8种社会经济状态表型的代表进行单变量MR分析。使用逆方差加权（IVW）方法作为主要分析方法来估计八种社会经济地位表型与GERD和BE风险之间的因果关系。然后，我们收集SNP的组合作为8种社会经济表型的复合代理，以基于IVWMVMR模型进行多变量MR（MVMR）分析。此外，使用两步MR调解分析来检查体重指数对关联的潜在调解，抑郁症（MDD），吸烟,酒精消费,和睡眠时间。
结果：该研究确定了三种对GERD有显著影响的社会经济状况。其中包括家庭收入[优势比（OR）：0.46；95％置信区间（95CI）：0.31-0.70]，教育程度（OR：0.23；95CI：0.18-0.29），以及招募时的汤森德剥夺指数（OR：1.57；95CI：1.04-2.37）。发现这些因素独立且主要影响GERD的遗传因果效应。此外，发现受教育程度对GERD的中介作用是由MDD介导的(介导比例:10.83%)。同样，受教育程度对BE的影响由MDD(介导比例:10.58%)和每日吸烟数量(介导比例:3.50%)介导.此外,观察到家庭收入对GERD的中介作用是由睡眠持续时间介导的(介导比例:9.75%)。
结论：这项MR研究揭示了社会经济地位与GERD或BE之间的联系，为食管癌和癌前病变的预防提供见解。
目的：使用孟德尔随机化（MR）探索这些疾病的患病率与社会经济状况之间的因果关系。
方法：我们最初筛选了单核苷酸多态性（SNPs），作为8种社会经济状态表型的代表进行单变量MR分析。使用逆方差加权（IVW）方法作为主要分析方法来估计八种社会经济地位表型与GERD和BE风险之间的因果关系。然后，我们收集SNP的组合作为8种社会经济表型的复合代理，以基于IVWMVMR模型进行多变量MR（MVMR）分析。此外，使用两步MR调解分析来检查体重指数对关联的潜在调解，抑郁症（MDD），吸烟,酒精消费,和睡眠时间。
结果：该研究确定了三种对GERD有显著影响的社会经济状况。其中包括家庭收入[优势比（OR）：0.46；95％置信区间（95CI）：0.31-0.70]，教育程度（OR：0.23；95CI：0.18-0.29），以及招募时的汤森德剥夺指数（OR：1.57；95CI：1.04-2.37）。发现这些因素独立且主要影响GERD的遗传因果效应。此外，发现受教育程度对GERD的中介作用是由MDD介导的(介导比例:10.83%)。同样，受教育程度对BE的影响由MDD(介导比例:10.58%)和每日吸烟数量(介导比例:3.50%)介导.此外,观察到家庭收入对GERD的中介作用是由睡眠持续时间介导的(介导比例:9.75%)。
结论：这项MR研究揭示了社会经济地位与GERD或BE之间的联系，为食管癌和癌前病变的预防提供见解。
