Evidence map›Paper›PMID 40361162›Full record

ArticleHuman genomics2025

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

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

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Article in Human genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
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3citing papers in PubMed
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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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3 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Tong LiDepartment of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Yingyue ZhangDepartment of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Xingzhi WangDepartment of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China. wang.xingzhi@hrbmu.edu.cn.
Qi LiuGuangdong Technion-Israel Institute of Technology, Shantou, 515036, China.
Xiaofei MaDepartment of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Manshu SuiDepartment of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.

Funding

BEIJING MEDICAL AWARD FOUDATION YXJL-2023-0866-0337
6 · The paper itself

Abstract

backgroundPrevious 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.

resultsSMR 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.

conclusionOur 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 registrationNot applicable.

Indexed as

Genetic Predisposition to DiseaseRenal Insufficiency, ChronicDNA MethylationGenome-Wide Association StudyHepatocyte Growth FactorHumansPolymorphism, Single NucleotideQuantitative Trait LociHepatocyte Growth FactorChronic kidney diseaseGeneMendelian randomizationPANoptosis

Identifiers

PMID40361162
PMCPMC12077045

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.