Mao Kun, Li Ang, Liu Haochen, Gao Yuntong, Wang Ziyan, Wang Xisu, Liu Shixuan, Gao Ziyuan, Quan Jiaqi, Shao Moyan, Liu Yunxi, Shi Liang, Zhang Bo, Zhang Tianxiao
Department of Epidemiology and Biostatistics, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.
Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.
Genes (Basel). 2025 Apr 29;16(5):523. doi: 10.3390/genes16050523.
Cholelithiasis is the most common disorder affecting the biliary system. Choline is an essential nutrient in the human diet and is crucial for the synthesis of neurotransmitters. Previous studies have suggested an association between choline metabolites and cholelithiasis. However, the underlying mechanisms remain unclear. This research aims to fill the knowledge gap regarding the role of choline metabolites in cholelithiasis.
Genetic data related to choline metabolites and other covariates were retrieved from the U.K. Biobank and IEU OpenGWAS database. Two-sample (TSMR) and multivariate Mendelian randomization (MVMR) analyses, mediation analysis, linkage disequilibrium score regression (LDSC), colocalization analysis, and enrichment analysis were performed.
A significant causal relationship was identified between serum level of sphingomyelin and cholelithiasis (-value = 0.0002). A protective causal effect was identified in MVMR analysis. The following mediated MR analysis indicated that only LDL mediated a large part of the causal relationship (59.18%). Seven genes, including , , , , , , and , were revealed to be colocalized with the causal signal between sphingomyelin and cholelithiasis.
The present study has identified a protective effect between sphingomyelin and cholelithiasis. This effect is largely mediated by LDL. The findings of this study offer valuable information for further exploration of the molecular mechanisms of cholelithiasis.
胆结石是影响胆道系统最常见的疾病。胆碱是人类饮食中的一种必需营养素，对神经递质的合成至关重要。先前的研究表明胆碱代谢物与胆结石之间存在关联。然而，其潜在机制仍不清楚。本研究旨在填补关于胆碱代谢物在胆结石中作用的知识空白。
从英国生物银行和IEU OpenGWAS数据库中检索与胆碱代谢物及其他协变量相关的遗传数据。进行了两样本（TSMR）和多变量孟德尔随机化（MVMR）分析、中介分析、连锁不平衡评分回归（LDSC）、共定位分析和富集分析。
确定了鞘磷脂血清水平与胆结石之间存在显著因果关系（P值 = 0.0002）。在MVMR分析中确定了一种保护因果效应。随后的中介MR分析表明，只有低密度脂蛋白（LDL）介导了大部分因果关系（59.18%）。包括[此处原文缺失基因名称]等七个基因被揭示与鞘磷脂和胆结石之间的因果信号共定位。
本研究确定了鞘磷脂与胆结石之间的保护作用。这种作用很大程度上由低密度脂蛋白介导。本研究结果为进一步探索胆结石的分子机制提供了有价值的信息。
