背景:越来越多的研究表明饮食因素与胃食管反流病(GERD)之间存在关联。然而,这些关联是否为因果关系,以及饮食因素影响GERD的潜在机制尚不清楚.
方法:进行了两步孟德尔随机化分析,以获得饮食因素的因果估计,血脂对GERD的影响。选择全基因组显著性水平上与13种膳食因素和5种血脂相关的独立遗传变异作为辅助变量。GERD的汇总统计数据来自欧洲生物信息学研究所,包括129,080例病例和473,524例对照。采用逆方差加权作为主要统计方法。MR-Egger截距测试,Cochran的Q测试,并进行留一法分析以评估可能的异质性和多效性。并使用Steiger滤波评估潜在的反向因果关系。
结果:逆方差加权方法的结果表明,遗传预测的猪肉总摄入量(OR=2.60,95%CI:1.21-5.58,p=0.0143),总面包摄入量(OR=0.68,95%CI:0.46-0.99,p=0.0497),谷物总摄入量(OR=0.42,95%CI:0.31-0.56,p=2.98E-06),奶酪总摄入量(OR=0.41,95%CI:0.27-0.61,p=1.06E-05)与GERD风险相关。多变量孟德尔随机化分析还揭示了谷物总摄入量之间的负相关,奶酪的总摄入量和GERD的风险,但调整吸烟后,猪肉总摄入量和面包总摄入量对GERD的影响消失,酒精消费,使用钙通道阻滞剂,BMI,身体活动水平,和生物性别(年龄调整)。此外,低密度脂蛋白胆固醇(LDL-C)的浓度与奶酪的总摄入量呈负相关,这调节了奶酪总摄入量对GERD的影响。LDL-C介导的比例为2.27%(95CI:1.57%,4.09%)。
结论:这项研究提供了证据,表明谷物总摄入量和奶酪总摄入量的增加将降低GERD的风险。此外,LDL-C介导总奶酪摄入量对GERD的因果效应。这些结果为饮食因素和血脂在GERD中的作用提供了新的见解。这有利于疾病预防。
BACKGROUND: Growing studies have indicated an association between dietary factors and gastroesophageal reflux disease (GERD). However, whether these associations refer to a causal relationship and the potential mechanism by which dietary factors affect GERD is still unclear.
METHODS: A two-step mendelian randomization analysis was performed to obtain causal estimates of dietary factors, blood lipids on GERD. Independent genetic variants associated with 13 kinds of dietary factors and 5 kinds of blood lipids at the genome-wide significance level were selected as instrumental variables. The summary statistics for GERD were obtained from European Bioinformatics Institute, including 129,080 cases and 473,524 controls. Inverse variance weighted was utilized as the main statistical method. MR-Egger intercept test, Cochran\'s Q test, and leave-one-out analysis were performed to evaluate possible heterogeneity and pleiotropy. And the potential reverse causality was assessed using Steiger filtering.
RESULTS: The results of the inverse variance weighted method indicated that genetically predicted total pork intake (OR = 2.60, 95% CI: 1.21-5.58, p = 0.0143), total bread intake (OR = 0.68, 95% CI: 0.46-0.99, p = 0.0497), total cereal intake (OR = 0.42, 95% CI: 0.31-0.56, p = 2.98E-06), and total cheese intake (OR = 0.41, 95% CI: 0.27-0.61, p = 1.06E-05) were associated with the risk of GERD. Multivariable Mendelian randomization analysis also revealed a negative association between total cereal intake, total cheese intake and the risk of GERD, but the effect of total pork intake and total bread intake on GERD disappeared after adjustment of smoking, alcohol consumption, use of calcium channel blockers, BMI, physical activity levels, and biological sex (age adjusted). Furthermore, the concentration of low-density lipoprotein cholesterol (LDL-C) is negatively correlated with total cheese intake, which mediates the impact of total cheese intake on GERD. The proportion mediated by LDL-C is 2.27% (95%CI: 1.57%, 4.09%).
CONCLUSIONS: This study provides evidence that an increase in total cereal intake and total cheese intake will decrease the risk of GERD. Additionally, LDL-C mediates the causal effect of total cheese intake on GERD. These results provide new insights into the role of dietary factors and blood lipids in GERD, which is beneficial for disease prevention.