海南医科大学学报2025，Vol.31Issue(3)：211-219,9.DOI:10.13210/j.cnki.jhmu.20240927.006
血液代谢物与糖尿病肾脏疾病因果关系的孟德尔随机化研究
A Mendelian randomized study on the causal relationship between blood metabolites and diabetic kidney disease
摘要
Abstract
Objective:To investigate the causal relationship between blood metabolites and the risk of diabetic kidney disease(DKD)by using two-sample Mendelian randomization analysis.Methods:A genome-wide association study(GWAS)involving 7 824 participants provided information on 486 human blood metabolites.The preliminary analysis used DKD GWAS data from a Finnish database containing 4 111 European cases and 308 539 controls.DKD outcome data for replication analysis were obtained from the IEU OpenGWAS project website and included 1 032 European cases and 452 280 controls.Inverse variance weighting method was used as the main analysis method,supplemented by MR-Egger and weighted median method.Multiple comparisons were conducted using false discovery rate to control the level of hypothesis testing.Sensitivity analysis was performed to evaluate the reliability of the results.In addition,linkage disequilibrium score regression,steiger test,replication and meta-analysis,and confounding analysis were performed to fully verify causality.Results:γ-Glutamyl-leucine(OR=3.71,95%CI:1.23-11.18,PIVW=0.019 6,PFDR=0.042),hydroxytryptophan(OR=4.55,95%CI:1.81-11.48,PIVW=0.001 3,PFDR=0.024),octanoylcarnitine(OR=1.99,95%CI:1.11-3.58,PIVW=0.020 7,PFDR=0.042),1,7-dimethyluric acid(OR=1.74,95%CI:1.04-2.90,PIVW=0.035 1,PFDR=0.045),bradykinin(OR=1.19,95%CI:1.01-1.40,PIVW=0.042 8,PFDR=0.047)and dihomo-linoleate(OR=7.23,95%CI:1.07-48.59,PIVW=0.042,PFDR=0.047)were positivelycorrelated with the risk of DKD.The results of sensitivity analysis were robust and there was no heterogeneity or horizontal pleiotropy.Conclusion:This study elucidates specific blood me-tabolites causally associated with DKD,providing potential targets for intervention and contributing to its early screening and pre-vention.关键词
血液代谢物/糖尿病肾脏疾病/因果推断/孟德尔随机化Key words
Blood metabolites/Diabetic kidney disease/Causal inference/Mendelian randomization分类
医药卫生引用本文复制引用
朱玲玲,钮杰宇,谭莹,佘云,余江毅,严倩华..血液代谢物与糖尿病肾脏疾病因果关系的孟德尔随机化研究[J].海南医科大学学报,2025,31(3):211-219,9.基金项目
This study was supported by the National Natural Science Foundation of China(82004286) （82004286）
Administration of Chinese Medicine of Jiangsu Province(ZT202206) （ZT202206）
Postgraduate Research&Practice Innovation Program of Jiangsu Province(SJCX23_0873) 国家自然科学基金项目(82004286) （SJCX23_0873）
江苏省中医药管理局项目(ZT202206) （ZT202206）
江苏省研究生实践创新计划项目(SJCX23_0873) （SJCX23_0873）
