Evidence map›Paper›PMID 39425076›Full record

ArticleBMC nephrology2024

Multi-scalar data integration decoding risk genes for chronic kidney disease.

Shiqi Ding, Jing Guo, Huimei Chen, Enrico Petretto

Abstract read
In one paragraph

Article in BMC nephrology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Shiqi DingThe NUS High School of Mathematics and Science , NUSH, 20 Clementi Ave 1, Singapore, Singapore.
Jing GuoProgramme in Cardiovascular and Metabolic Disorders (CVMD) and Centre for Computational Biology (CCB), Duke-NUS Medical School, 8 College Road, Singapore, Singapore.
Huimei ChenProgramme in Cardiovascular and Metabolic Disorders (CVMD) and Centre for Computational Biology (CCB), Duke-NUS Medical School, 8 College Road, Singapore, Singapore. huimei.chen@duke-nus.edu.sg.
Enrico PetrettoProgramme in Cardiovascular and Metabolic Disorders (CVMD) and Centre for Computational Biology (CCB), Duke-NUS Medical School, 8 College Road, Singapore, Singapore.

Funding

Ministry of Education (ARC, MOE) of Singapore AcRF Tier 2 funding (T2EP30221-0013)Singapore National Medical Research Council OFLCG22may-0011
6 · The paper itself

Abstract

backgroundChronic Kidney Disease (CKD) impacts over 10% of the global population, and recent advancements in high-throughput analytical technologies are uncovering the complex physiology underlying this condition. By integrating Genome-Wide Association Studies (GWAS), RNA sequencing (RNA-seq/RNA array), and single-cell RNA sequencing (scRNA-seq) data, our study aimed to explore the genes and cell types relevant to CKD traits.

methodsGWAS summary data for end-stage renal failure (ESRD) and decreased eGFR (CKD) with or without diabetes and (micro)proteinuria were obtained from the GWAS Catalog and the UK Biobank (UKB) database. Two gene Expression Omnibus (GEO) transcriptome datasets were used to establish glomerular and tubular gene expression differences between CKD patients and healthy individuals. Two scRNA-seq datasets were utilized to obtain the expression of key genes at the single-cell level. The expression profile, differentially expressed genes (DEGs), gene-gene interaction, and pathway enrichment were analysed for these CKD risk genes.

resultsA total of 779 distinct SNPs were identified from GWAS across different CKD traits, involving 681 genes. While many of these risk genes are specific to the CKD traits of renal failure, decreased eGFR, and (micro)proteinuria, they share common pathways, including extracellular matrix (ECM). ECM modeling was enriched in upregulated glomerular and tubular DEGs from CKD kidneys compared to healthy controls, with the expression of relevant collagen genes, such as COL1A2, prevalent in fibroblasts/myofibroblasts. Additionally, immune responses, including T cell differentiation, were dysregulated in CKD kidneys. The late podocyte signature gene THSD7A was enriched in podocytes but downregulated in CKD. We also highlighted that the regulated risk genes of CKD are mainly expressed in tubular cells and immune cells in the kidney.

conclusionsOur integrated analysis highlight the genes, pathways, and relevant cell types associational with the pathogenesis of kidney traits, as a basis for further mechanistic studies to understand the pathogenesis of CKD.

Indexed as

Genome-Wide Association StudyRenal Insufficiency, ChronicGenetic Predisposition to DiseaseGlomerular Filtration RateHumansKidney Failure, ChronicPolymorphism, Single NucleotideSequence Analysis, RNASingle-Cell AnalysisTranscriptomeCKDGWASIntegrated analysisRNA-seqscRNA-seq

Identifiers

PMID39425076
PMCPMC11489995

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

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 Socratic graph.