■慢性肾脏病(CKD)通常伴随着身体代谢谱的改变,然而,这些代谢变化在CKD发病中的致病作用仍是一个争论的话题.这项研究通过利用来自486个血液代谢物的全基因组关联研究(GWAS)的结果,调查了代谢物与CKD之间的因果关系。采用批量双样本孟德尔随机化(MR)分析。基于与CKD有因果关系的代谢物,我们使用富集分析更深入地研究了可能有助于CKD发生发展的代谢途径.
■在进行孟德尔随机化分析时,我们将486个代谢性状的GWAS数据作为暴露变量,同时使用GWAS数据根据血清肌酐(eGFRcrea)估计肾小球滤过率,微量白蛋白尿,和来自CKDGen联盟的尿白蛋白-肌酐比值(UACR)作为结果变量。使用逆方差加权(IVW)分析来鉴定与结果有因果关系的代谢物。使用Bonferroni校正,筛选具有更稳健因果关系的代谢物。此外,IVW阳性结果补充了加权中位数,MR-Egger,加权模式,和简单的模式。此外,我们使用CochranQ检验进行敏感性分析,MR-Egger截距测试,MR-PRESSO,和漏检(LOO)测试。使用两个数据库进行途径富集分析,KEGG和SMPDB,合格的代谢物。
■在孟德尔随机分组(MR)分析中,在完成逆方差加权(IVW)方法后,敏感性分析,和方向性一致性检查,发现78种代谢物符合标准。以下四种代谢物满足Bonferroni校正:甘露糖,N-乙酰鸟氨酸,甘氨酸,和胆红素(Z,Z),甘露糖与CKD的所有结局都有因果关系。通过途径富集分析,我们确定了促进CKD发生和进展的8个代谢途径.
■根据目前的分析,甘露糖符合Bonferroni校正,与CKD有因果关系,eGFRcrea,微量白蛋白尿,和UACR。作为CKD诊断和治疗的潜在靶点,甘露糖在CKD的发生、发展中起重要作用。
UNASSIGNED: Chronic kidney disease (CKD) is often accompanied by alterations in the metabolic profile of the body, yet the causative role of these metabolic changes in the onset of CKD remains a subject of ongoing debate. This
study investigates the causative links between metabolites and CKD by leveraging the results of genomewide association
study (GWAS) from 486 blood metabolites, employing bulk two-sample Mendelian randomization (MR) analyses. Building on the metabolites that exhibit a causal relationship with CKD, we delve deeper using enrichment analysis to identify the metabolic pathways that may contribute to the development and progression of CKD.
UNASSIGNED: In conducting the Mendelian randomization analysis, we treated the GWAS data for 486 metabolic traits as exposure variables while using GWAS data for estimated glomerular filtration rate based on serum creatinine (eGFRcrea), microalbuminuria, and the urinary albumin-to-creatinine ratio (UACR) sourced from the CKDGen consortium as the outcome variables. Inverse-variance weighting (IVW) analysis was used to identify metabolites with a causal relationship to outcome. Using Bonferroni correction, metabolites with more robust causal relationships are screened. Additionally, the IVW-positive results were supplemented with the weighted median, MR-Egger, weighted mode, and simple mode. Furthermore, we performed sensitivity analyses using the Cochran Q test, MR-Egger intercept test, MR-PRESSO, and leave-one-out (LOO) test. Pathway enrichment analysis was conducted using two databases, KEGG and SMPDB, for eligible metabolites.
UNASSIGNED: During the batch Mendelian randomization (MR) analyses, upon completion of the inverse-variance weighted (IVW) approach, sensitivity analysis, and directional consistency checks, 78 metabolites were found to meet the criteria. The following four metabolites satisfy Bonferroni correction:
mannose, N-acetylornithine, glycine, and bilirubin (Z, Z), and
mannose is causally related to all outcomes of CKD. By pathway enrichment analysis, we identified eight metabolic pathways that contribute to CKD occurrence and progression.
UNASSIGNED: Based on the present analysis, mannose met Bonferroni correction and had causal associations with CKD, eGFRcrea, microalbuminuria, and UACR. As a potential target for CKD diagnosis and treatment,
mannose is believed to play an important role in the occurrence and development of CKD.