基于两样本孟德尔随机化方法分析血液代谢物与慢性肾病的因果关系  

Causal relationship between human blood metabolites and chronic kidney disease using two-sample Mendelian randomization method

作　　者：王婷 蒋舟 曾平 WANG Ting;JIANG Zhou;ZENG Ping(School of Public Health,Xuzhou Medical University,Jiangsu Xuzhou 221004,China)

机构地区：[1]徐州医科大学公共卫生学院,江苏徐州221004

出　　处：《江苏预防医学》2022年第2期124-128,共5页Jiangsu Journal of Preventive Medicine

基　　金：江苏省自然科学基金(BK20181472);徐州市社会发展项目(KC20062);徐州医科大学青年科技创新团队培育计划资助项目(TD202008)。

摘　　要：目的利用孟德尔随机化方法,探究486种血液代谢物与慢性肾病的因果关系。方法血液代谢物和慢性肾病全基因组关联分析汇总数据均来自于网络公开数据库,主要采用逆方差加权分析法(inverse-variance weighting,IVW),探究每种血液代谢物与慢性肾病之间的因果关系,并以MR-Egger回归、加权中位数法、基于众数估计法等进行敏感性分析。结果发现1个与慢性肾病具有直接因果关联的代谢物,即N-乙酰鸟氨酸;2个可能具有直接因果关联的代谢物,即甘露糖和甜菜碱;3个潜在风险因子,即脯氨酸、癸酸酯、硬脂酰胺。6个代谢物中,甜菜碱(OR=0.50,95%CI:0.39~0.66)和癸酸酯(OR=0.55,95%CI:0.37~0.80)降低慢性肾病患病风险,N-乙酰鸟氨酸(OR=1.30,95%CI:1.24~1.36)、甘露糖(OR=1.62,95%CI:1.30~2.00)、脯氨酸(OR=1.47,95%CI:1.19~1.82)和硬脂酰胺(OR=1.40,95%CI:1.16~1.68)增加慢性肾病患病风险。结论6种代谢物可能与慢性肾病存在因果关联,可为探索慢性肾病的发病机制及早期筛检和治疗提供参考。Objective To explore the causal relationship between 486 blood metabolites and chronic kidney disease(CKD)by two-sample Mendelian randomization method.Methods The genome-wide association studies summary-level data associated with blood metabolites and CKD were obtained from online database.The inverse variance weighting(IVW)method was used to explore the causal association between each blood metabolite and CKD,with three other models of MR-Egger regression analysis,weighted median estimation(WME)analysis,and mode based estimation(MBE)analysis for sensitivity analysis.Results There was 1 metabolite of N-acetylornithine was identified to have a causal relationship with CKD;while 2 metabolites of mannose and betaine showed possible direct causal relationship;and 3 metabolites of potential risk predictors such as proline,caprate and stearamide were identified.Among above 6 metabolites,betaine(OR=0.50,95%CI:0.39-0.66)and caprate(OR=0.55,95%CI:0.37-0.80)may reduce the risk of CKD;while N-acetylornithine(OR=1.30,95%CI:1.24-1.36),mannose(OR=1.62,95%CI:1.30-2.00),proline(OR=1.47,95%CI:1.19-1.82)and stearamide(OR=1.40,95%CI:1.16-1.68)increased the risk of CKD.Conclusion A total of 6 metabolites are identified to have possible causal correlation with CKD,which can provide reference for exploring the pathogenesis mechanism together with early screening and treatment.

关 键 词：孟德尔随机化分析 血液代谢物 慢性肾病 因果关联 

分 类 号：R69[医药卫生—泌尿科学]