The causal relationships between plasma metabolites and cholelithiasis/cholecystitis risks remain elusive. Using two-sample Mendelian randomization, we found that genetic proxied plasma campesterol level showed negative correlation with the risk of both cholelithiasis and cholecystitis. Furthermore, the increased risk of cholelithiasis is correlating with the increased level of plasma campesterol. Lastly, genetic colocalization study showed that the leading SNP, rs4299376, which residing at the ABCG5/ABCG8 gene loci, was shared by plasma campesterol level and cholelithiasis, indicating that the aberrant transportation of plant sterol/cholesterol from the blood stream to the bile duct/gut lumen might be the key in preventing cholesterol gallstone formation.

中文翻译：

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血浆菜油甾醇和 ABCG5/ABCG8 基因位点对胆石症和胆囊炎风险的影响：来自孟德尔随机化和共定位分析的证据

血浆代谢物与胆石症/胆囊炎风险之间的因果关系仍然难以捉摸。使用双样本孟德尔随机化，我们发现遗传代理的血浆菜油甾醇水平与胆石症和胆囊炎的风险呈负相关。此外，胆石症风险的增加与血浆菜油甾醇水平的增加相关。最后，遗传共定位研究表明，位于 ABCG5/ABCG8 基因位点的主要 SNP rs4299376 与血浆菜油甾醇水平和胆石症共有，表明植物甾醇/胆固醇从血流到胆管的异常运输/肠腔可能是预防胆固醇胆结石形成的关键。