Su Chen'guang, Liao Zheng, Li Hewen, Pei Yinxuan, Wang Zixiang, Li Jian, Liu Jinlong
Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, China.
Department of Minimally Invasive Spine Surgery, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, China.
Front Genet. 2024 Dec 5;15:1428334. doi: 10.3389/fgene.2024.1428334. eCollection 2024.
Numerous observational studies have shown a potential association between metabolic dysfunction-associated steatotic liver disease (MASLD) and gastroesophageal reflux disease (GERD). However, causality is unclear. This study utilized genome-wide association study (GWAS) genetic data to explore the causal relationship between MASLD and GERD in European and East Asian populations.
This study utilized a bidirectional, two-sample Mendelian randomization (MR) approach. All disease data were obtained from the GWAS database, and single nucleotide polymorphisms strongly associated with exposure were selected as instrumental variables. The inverse variance weighted (IVW) method is primarily utilized to evaluate the causal relationship between exposure and outcome. Finally, sensitivity analyses were performed to ensure the robustness of the results.
The IVW estimates indicated that non-alcoholic fatty liver disease (NAFLD) (odds ratio (OR) = 1.054, 95% confidence interval (CI), 0.966-1.150, = 0.236) and percent liver fat (OR = 0.977, 95% CI, 0.937-1.018, = 0.258) in European population were not linked to a higher risk of GERD. However, GERD in European population was associated with an increased risk of NAFLD (OR = 1.485, 95% CI, 1.274-1.729, < 0.001) and percent liver fat (OR = 1.244, 95% CI, 1.171-1.321, < 0.001). In addition, the IVW analysis in East Asian population showed that alanine aminotransferase (ALT) was associated with an increased risk of GERD (OR = 2.305, 95% CI, 1.241-4.281, = 0.008), whereas aspartate aminotransferase (AST) had no causal effects on GERD risk (OR = 0.973, 95% CI, 0.541-1.749, = 0.926). Furthermore, the associations between GERD and ALT (OR = 1.007, 95% CI, 0.998-1.015, = 0.123) or AST (OR = 1.004, 95% CI, 0.997-1.012, = 0.246) were not significant. After removing outliers, a significant correlation between GERD and ALT was observed (OR = 1.009, 95% CI, 1.001-1.016, = 0.020).
There was reverse causality between MASLD and GERD in European population, while there was bidirectional causality between a proxie for MASLD (ALT) and GERD in East Asian population. This study can provide novel insights into cross-ethnic genetic research on MASLD and GERD.
众多观察性研究显示，代谢功能障碍相关脂肪性肝病（MASLD）与胃食管反流病（GERD）之间可能存在关联。然而，因果关系尚不清楚。本研究利用全基因组关联研究（GWAS）的遗传数据，探讨欧洲和东亚人群中MASLD与GERD之间的因果关系。
本研究采用双向双样本孟德尔随机化（MR）方法。所有疾病数据均来自GWAS数据库，并选择与暴露密切相关的单核苷酸多态性作为工具变量。主要采用逆方差加权（IVW）方法评估暴露与结局之间的因果关系。最后，进行敏感性分析以确保结果的稳健性。
IVW估计表明，欧洲人群中的非酒精性脂肪性肝病（NAFLD）（比值比（OR）=1.054，95%置信区间（CI），0.966 - 1.150，P = 0.236）和肝脏脂肪百分比（OR = 0.977，95%CI，0.937 - 1.018，P = 0.258）与GERD风险升高无关。然而，欧洲人群中的GERD与NAFLD风险增加相关（OR = 1.485，95%CI，1.274 - 1.729，P < 0.001）和肝脏脂肪百分比（OR = 1.244，95%CI，1.171 - 1.321，P < 0.001）。此外，东亚人群的IVW分析显示，丙氨酸氨基转移酶（ALT）与GERD风险增加相关（OR = 2.305，95%CI，1.241 - 4.281，P = 0.008），而天冬氨酸氨基转移酶（AST）对GERD风险无因果效应（OR = 0.973，95%CI，0.541 - 1.749，P = 0.926）。此外，GERD与ALT（OR = 1.007，95%CI，0.998 - 1.015，P = 0.123）或AST（OR = 1.004，95%CI，0.997 - 1.012，P = 0.246）之间的关联不显著。去除异常值后，观察到GERD与ALT之间存在显著相关性（OR = 1.009，95%CI，1.001 - 1.016，P = 0.020）。
欧洲人群中MASLD与GERD之间存在反向因果关系，而东亚人群中MASLD的一个替代指标（ALT）与GERD之间存在双向因果关系。本研究可为MASLD和GERD的跨种族遗传研究提供新的见解。
