双向孟德尔随机化分析总胆固醇升高风险与胆石症发生风险的关系
Association between the risk of increase in total cholesterol and the risk of cholelithiasis:A bidirectional Mendelian randomization study
赵伟伟 1杜晓旭 2戈宏焱3
作者信息
- 1. 内蒙古民族大学临床医学院,内蒙古 通辽 028000;兴平市汤坊镇卫生院,陕西 兴平 713100
- 2. 内蒙古民族大学临床医学院,内蒙古 通辽 028000
- 3. 内蒙古民族大学医学院,内蒙古 通辽 028000
- 折叠
摘要
目的 运用双向孟德尔随机化评估总胆固醇升高风险与胆石症发生风险之间的关联.方法 总胆固醇与胆石症相关的单核苷酸多态性数据来自open gwas公共数据库,对基于全基因组相关联研究(GWAS)的所有汇总数据进行二次数据分析,分别选择与总胆固醇或者胆石症密切关联的遗传位点作为暴露或者结局变量,用Egger回归法、加权中位数法、IVW随机效应模型、IVW固定效应模型等方法进行双向孟德尔随机化分析,以OR值评价总胆固醇和胆石症之间的因果关系.结果 以总胆固醇为暴露、胆石症为结局,去除异质性前总胆固醇-胆石症的总体OR=0.91,95%CI:0.85～0.97;去除异质性后总胆固醇-胆石症的总体OR=0.93,95%CI:0.89～0.97.以胆石症为暴露、总胆固醇为结局,去除异质性前胆石症-总胆固醇的总体OR=0.20,95%CI:0.06～0.65;去除异质性后胆石症-总胆固醇的总体OR=0.28,95%CI:0.10～0.83.基因预测的总胆固醇和胆石症之间存在双向因果关系.结论 本研究证实了总胆固醇与胆石症之间的双向因果关系,随着遗传上有关能使总胆固醇水平升高的等位基因的增加,发生胆石症的风险降低.反之,随着遗传上有关能使胆石症发病增高的等位基因的增加,总胆固醇水平升高的风险降低.
Abstract
Objective To investigate the association between the risk of increase in total cholesterol(TC)and the risk of cholelithiasis by using bidirectional Mendelian randomization(MR).Methods The open gwas public database was used to obtain the single nucleotide polymorphism data associated with TC and cholelithiasis,and a secondary data analysis was performed for all summary data of genome-wide association studies.The genetic loci closely associated with TC or cholelithiasis were selected as exposure or outcome variables,and the bidirectional MR analysis was performed using the methods such as Egger regression,Weighted median,IVW random effects model,and IVW fixed effects model,with odds ratio(OR)values for evaluating the causal relationship between TC and cholelithiasis.Results With TC as the exposure and cholelithiasis as the outcome,TC-cholelithiasis had an overall OR value of 0.91(95%confidence interval[CI]:0.85—0.97)before elimination of heterogeneity and 0.93(95%CI:0.89—0.97)after elimination of heterogeneity.With cholelithiasis as the exposure and TC as the outcome,TC-cholelithiasis had an overall OR value of 0.20(95%CI:0.06—0.65)before elimination of heterogeneity and 0.28(95%CI:0.10—0.83)after elimination of heterogeneity.There was a bidirectional causal relationship between genetically predicted TC and cholelithiasis.Conclusion This study confirms the bidirectional causal relationship between TC and cholelithiasis.The risk of cholelithiasis decreases with the increase in alleles associated with the elevation of TC level;on the contrary,the risk of elevated TC level decreases with the increase in alleles associated with the onset of cholelithiasis.
关键词
总胆固醇/胆石症/双向孟德尔随机化分析Key words
Total Cholesterol/Cholelithiasis/Bidirectional Mendelian Randomization Analysis引用本文复制引用
出版年
2024
国家科技期刊平台
NSTL
万方数据