Targeted multi-layer analysis of PANoptosis-associated genes in the etiology of chronic kidney disease.

IF 3.8 3区医学 Q2 GENETICS & HEREDITY

Human Genomics Pub Date : 2025-05-13 DOI:10.1186/s40246-025-00768-z

Tong Li, Yingyue Zhang, Xingzhi Wang, Qi Liu, Xiaofei Ma, Manshu Sui

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引用次数: 0

Abstract

Background: Previous studies have examined the cellular and molecular interactions between chronic kidney disease (CKD) and PANoptosis, yet the genetic underpinnings remain unclear.

Materials: Data at the summary level regarding the methylation, gene expression, and protein levels associated with PANoptosis were obtained from quantitative trait locus (QTL) studies. Genome-wide association study (GWAS) summary statistics for CKD were derived from a GWAS study, supplemented by a replication dataset from the FinnGen database. Genetic variants proximal to or within genes involved in PANoptosis, which showed robust associations with CKD, were utilized as instrumental variables. These variants were the subjected to SMR analysis to explore their causal relationship. The associations among QTLs were systematically analyzed. Additionally, a colocalization analysis was conducted to ascertain whether the signals identified corresponded to a shared genetic basis.

Results: SMR and colocalization analysis revealed 28 methylation sites and 5 genes associated with CKD.Notably, cg01304814 (PRKAR2A) and cg09177106, cg15114474 (CCND1) were inversely associated with CKD risk. Integrating mQTL and eQTL data, we identified four genes (CCND1, GUCY2D, HGF, MADD) causally associated with CKD, with a positive correlation between HGF gene expression and protein levels.

Conclusion: Our results provide evidence for the PANoptosis-related genes in the pathogenesis of CKD. Notably, PRKAR2A, HGF, CCND1 and MADD, emerged as potential mediators in the pathogenesis of CKD.

Trial registration: Not applicable.

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慢性肾脏疾病病因中panoposis相关基因的靶向多层分析。

背景：先前的研究已经研究了慢性肾脏疾病（CKD）和PANoptosis之间的细胞和分子相互作用，但其遗传基础尚不清楚。材料：与PANoptosis相关的甲基化、基因表达和蛋白质水平的汇总数据来自数量性状位点（QTL）研究。CKD的全基因组关联研究（GWAS）汇总统计数据来源于一项GWAS研究，并辅以FinnGen数据库的复制数据集。与PANoptosis相关的基因近端或内部的遗传变异显示出与CKD的强烈关联，被用作工具变量。对这些变异进行SMR分析，探讨其因果关系。系统分析qtl间的相关性。此外，还进行了共定位分析，以确定所识别的信号是否与共享的遗传基础相对应。结果：SMR和共定位分析显示28个甲基化位点和5个与CKD相关的基因。值得注意的是，cg01304814 （PRKAR2A）和cg09177106、cg15114474 （CCND1）与CKD风险呈负相关。整合mQTL和eQTL数据，我们发现4个基因（CCND1、GUCY2D、HGF、MADD）与CKD有因果关系，HGF基因表达与蛋白水平呈正相关。结论：本研究结果为CKD发病机制中panoposis相关基因的存在提供了依据。值得注意的是，PRKAR2A、HGF、CCND1和MADD被认为是CKD发病机制的潜在介质。试验注册：不适用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human Genomics GENETICS & HEREDITY-

CiteScore

6.00

自引率

2.20%

发文量

审稿时长

11 weeks

期刊介绍： Human Genomics is a peer-reviewed, open access, online journal that focuses on the application of genomic analysis in all aspects of human health and disease, as well as genomic analysis of drug efficacy and safety, and comparative genomics. Topics covered by the journal include, but are not limited to: pharmacogenomics, genome-wide association studies, genome-wide sequencing, exome sequencing, next-generation deep-sequencing, functional genomics, epigenomics, translational genomics, expression profiling, proteomics, bioinformatics, animal models, statistical genetics, genetic epidemiology, human population genetics and comparative genomics.