Appraising the causal effects of circulating micronutrients on liver cirrhosis:Evidence from large-scale Mendelian randomization analysis  

作　　者：Junlong Lin Jialin Chen Zhichao Li Baifeng Qian Yunpeng Hua 

机构地区：[1]Department of Liver Surgery,The First Affiliated Hospital,Sun Yat-sen University,Guangzhou,Guangdong,China

出　　处：《Portal Hypertension & Cirrhosis》2024年第3期160-170,共11页门静脉高压与肝硬化（英文）

基　　金：Guangdong Basic and Applied Basic Research Foundation,Grant/Award Numbers:2023A1515012531,2022A1515010537;Guangzhou Science and Technology Project,Grant/Award Number:2024B03J1256。

摘　　要：Aims:Observational research has identified links between micronutrient levels and chronic liver disease.However,the lack of randomized controlled experiments has impeded the ability to establish a cause-and-effect connection regarding micronutrients and cirrhosis of the liver.This Mendelian randomization(MR)analysis aimed to examine the causal impact of micronutrients on liver cirrhosis.Methods:We selected genetic instrumental variables related to 12 micronutrients from genome-wide studies on individuals of European descent,covering an array of over 9,851,867 single nucleotide polymorphisms and 460,351 participants.Data from patients with cirrhosis in the FinnGen database(https://www.finngen.fi/fi)were used.A two-sample MR approach was employed to establish genetically causal estimates.Primary analyses used random effects and inverse variance weighted(IVW)methods,with additional sensitivity analyses for validation.MR–Egger intercept analysis and Cochran's Q test assessed horizontal pleiotropy and heterogeneity.Furthermore,multivariable Mendelian randomization(MVMR)was conducted to address potential confounding variables.Results:IVW and weighted median methods showed that most micronutrients included were not significantly associated with a genetic susceptibility to liver cirrhosis.However,MR analysis demonstrated a significant association between circulating vitamin D levels and a reduced risk of liver cirrhosis(odds ratio IVW=0.53,p<0.010).TheMR–Egger intercept showed no evidence of horizontal pleiotropy(p=0.178),whereas Cochran's Q test found no heterogeneity(p=0.799).Furthermore,MVMR analysis confirmed vitamin D was identified as a factor that independently mitigates the risk of liver cirrhosis.Conclusion:This research constitutes the most comprehensive MR investigation in this field,providing evidence supporting a protective link between circulating vitamin D levels and cirrhosis incidence.It suggests that maintaining sufficient vitamin D could be a cost-effective strategy for early intervention in liver

关 键 词：liver cirrhosis Mendelian randomization MICRONUTRIENT vitamin D 

分 类 号：R575.2[医药卫生—消化系统]