Abstract：
Aims: Dietary habits are reported to be associated with Barrett\'s esophagus (BE) risk; however, whether there is a causal relationship remains controversial. Here, we systematically examined the causal effects of genetically predicted dietary habits on BE risk through a Mendelian randomization (MR) analysis approach. Methods: Data for exposures were obtained from the UK Biobank (UKB), while the summary-level data for outcomes were obtained from a large sample-size GWAS meta-analysis. Genetic variants associated with 17 ordinary dietary habits at the genome-wide significance level were regarded as instrumental variables (IVs). Univariable and multivariable MR analyses were conducted to explore the causal relationships between dietary habits and BE risk. Sensitivity analyses were implemented to evaluate robustness of the results and determine the potential pleiotropy bias. Results: Univariable MR (UVMR) analysis showed that genetic predisposition to alcohol intake frequency, cooked vegetable intake, beef intake, bread intake, fresh fruit intake, salad/raw vegetable intake, and dried fruit intake were associated with BE risk, with all P values <0.05. After adjusting confounders, the effects of four dietary habits on BE risk persisted; multivariable MR (MVMR) analysis revealed that alcohol intake frequency (adjusted odds ratio (OR) = 1.74 (1.34, 2.27); P = 3.42 × 10-5) was causally associated with higher BE risk, the cooked vegetable intake (adjusted OR = 2.64 (1.16, 5.97); P = 0.02) had suggestively increased BE risk, while higher consumption of bread (adjusted OR = 0.54 (0.32-0.91); P = 0.02) and fresh fruit (adjusted OR = 0.34 (0.15, 0.77); P = 0.01) were suggestively associated with lower BE risk. Conclusions: These MR analyses demonstrate evidence of causal relationships between dietary habits and BE risk. These findings provide new insights into targeted dietary intervention strategies for BE prevention.
摘要：
目的：据报道，饮食习惯与Barrett食管（BE）风险有关；然而，是否存在因果关系仍然存在争议。这里,我们通过孟德尔随机化(MR)分析方法,系统地研究了遗传预测的饮食习惯对BE风险的因果影响.方法：暴露数据来自英国生物库(UKB)，而结局的汇总数据来自大样本量GWAS荟萃分析.在全基因组显著性水平上与17种普通饮食习惯相关的遗传变异被视为工具变量(IVs)。进行了单变量和多变量MR分析，以探讨饮食习惯与BE风险之间的因果关系。实施敏感性分析以评估结果的稳健性并确定潜在的多效性偏差。结果:单变量MR(UVMR)分析显示,饮酒频率的遗传易感性,煮熟的蔬菜摄入量，牛肉摄入量，面包摄入量，新鲜水果的摄入量，沙拉/生蔬菜摄入量，干果摄入量与BE风险相关，所有P值<0.05。在调整混杂因素后，四种饮食习惯对BE风险的影响持续存在；多变量MR（MVMR）分析显示，饮酒频率（校正比值比（OR）=1.74（1.34，2.27）；P=3.42×10-5）与较高的BE风险有因果关系。煮熟的蔬菜摄入量（调整后的OR=2.64（1.16，5.97）；P=0.02）暗示性增加了BE风险，而较高的面包消费量(校正后OR=0.54(0.32-0.91);P=0.02)和新鲜水果消费量(校正后OR=0.34(0.15,0.77);P=0.01)提示与较低的BE风险相关。结论：这些MR分析证明了饮食习惯与BE风险之间存在因果关系。这些发现为BE预防的针对性饮食干预策略提供了新的见解。
