孟德尔随机化研究揭示饮茶与胆石症之间的因果关系  

Mendelian randomized study reveals the causal relationship between tea drinking and cholelithiasis

作　　者：陈紫英 牛翊霖 倪明星 梁会营 CHEN Zi-ying;NIU Yi-lin;NI Ming-xing;LIANG Hui-ying(School of Public Health,Southern Medical University,Guangzhou,Guangdong 510515,China;不详)

机构地区：[1]南方医科大学公共卫生学院,广东广州510515 [2]中国医科大学公共卫生学院 [3]南方医科大学附属广东省人民医院(广东省医学科学院)大数据中心,广东广州510080

出　　处：《现代预防医学》2024年第7期1181-1186,共6页Modern Preventive Medicine

摘　　要：目的采用双向孟德尔随机化方法评估饮茶与胆石症之间的因果关系。方法饮茶的遗传工具是从UK Biobank全基因组关联研究(genome-wide association study,GWAS)中447485名参与者确定的,其中共采用与饮茶相关的32个单核苷酸多态性(single nucleotide polymorphism,SNP)进行两样本孟德尔随机化分析以评估饮茶与胆石症之间的因果关系。胆石症的数据来自Finngen联盟公开提供的35712名胆石症患者和273442名对照人群的GWAS数据。本研究以inverse-variance weighted(IVW)为主要方法估计因果关系,并进行敏感性分析以确保结果的稳健性。最后,采用反向孟德尔随机化分析验证是否存在反向关联。结果饮茶与胆石症存在因果关系。在IVW方法中,饮茶每增加一个标准差(2.85杯/d),胆石症的发生风险减低26.1%(OR=0.739,95%CI:0.536~0.990)。在weighted mode中也得到了相似的结果(OR=0.652,95%CI:0.458~0.928),但没有证据证明存在反向关联(IVW:P>0.05)。结论双向孟德尔随机化分析提供的遗传证据表明,饮茶的增加会降低胆石症发生的风险,但没有证据证明存在反向关联。Objective To evaluate the causal relationship between tea drinking and cholelithiasis by two-way Mendelian randomization.Methods The instrumental variables for tea drinking were determined from 447485 participants in the UK Biobank genome-wide association study(GWAS).A total of 32 single nucleotide polymorphisms(SNPs)associated with tea drinking were used for two-sample Mendelian randomized analysis to evaluate the causal relationship between tea drinking and cholelithiasis.Cholelithiasis data were obtained from GWAS data of 35712 cholelithiasis patients and 273442 controls publicly available from the Finnegan Alliance.In this study,inverse variance weighted(IVW)was used as the main method to estimate causality,and sensitivity analysis was carried out to ensure the robustness of the results.Finally,reverse Mendelian randomization analysis was used to verify whether there was a reverse correlation.Results There was a causal relationship between tea drinking and cholelithiasis.In the IVW method,each additional standard deviation(2.85 cups/day)of tea consumption reduced the risk of cholelithiasis by 26.1%(OR=0.739,95%CI:0.536-0.990).Similar results were obtained in weighted mode(OR=0.652,95%CI:0.458-0.928),but there was no evidence to prove reverse correlation(IVW:P>0.05).Conclusion The genetic evidence provided by two-way Mendelian randomized analysis shows that the increase of tea drinking reduces the risk of cholelithiasis,but there is no evidence of reverse association.

关 键 词：饮茶 胆石症 孟德尔随机化 全基因组关联研究 因果关系 

分 类 号：R575.62[医药卫生—消化系统]