Evidence map›Paper›PMID 40898345›Full record

ArticlePediatric rheumatology online journal2025

Evaluating the causal effect of circulating proteome on the risk of Juvenile idiopathic arthritis: an omics pipeline study.

Xinglin Wu, Qiang Luo, Xiwen Luo, Dawei Liu, Fengming Li, Chenxi Ma, Xuemei Tang

Abstract read
In one paragraph

Article in Pediatric rheumatology online journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

7 authors.

Xinglin WuDepartment of Rheumatology and Immunology, Children's Hospital of Chongqing Medical University, No. 136, Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, China.
Qiang LuoDepartment of Rheumatology and Immunology, Children's Hospital of Chongqing Medical University, No. 136, Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, China.
Xiwen LuoDepartment of Rheumatology and Immunology, Children's Hospital of Chongqing Medical University, No. 136, Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, China.
Dawei LiuDepartment of Rheumatology and Immunology, Children's Hospital of Chongqing Medical University, No. 136, Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, China.
Fengming LiDepartment of Rheumatology and Immunology, Children's Hospital of Chongqing Medical University, No. 136, Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, China.
Chenxi MaDepartment of Rheumatology and Immunology, Children's Hospital of Chongqing Medical University, No. 136, Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, China.
Xuemei TangDepartment of Rheumatology and Immunology, Children's Hospital of Chongqing Medical University, No. 136, Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, China. tangxuemei2008@163.com.

Funding

National Key Research and Development Program of China No. 2021YFC2702003
6 · The paper itself

Abstract

backgroundGenome-wide association studies (GWAS) have pinpointed a multitude of risk loci associated with Juvenile Idiopathic Arthritis (JIA), but it is challenging to decipher novel plasma proteins. To address this, we applied an integrative omics pipeline to uncover novel proteins associated with JIA risk.

methodsIn this research, we utilized an integrative omics method to identify new plasma proteins associated with JIA. Complementary results from an independent cohort were analyzed through Whole Genome Sequencing (WGS), single-cell RNA sequencing (scRNA-seq), and bulk RNA sequencing (bulk RNA-seq) at the Children's Hospital of Chongqing Medical University to validate the reliability of the identified novel proteins. Additionally, to assess the therapeutic potential of novel proteins, we performed Phe-WAS and conducted an extensive review of existing literature using PubMed and Web of Science.

resultsAn integrative omics pipeline analysis identified ERAP2 as having putatively causal effects on JIA. In the fourth step of Summary-data-based Mendelian randomization analysis, we discovered that the SNP rs2927608 and rs2910686 can regulate the expression of the ERAP2 gene, thereby regulating the protein content of both ERAP2 and ERAP1. WGS analysis also detected two potentially pathogenic mutations on ERAP2 in sJIA patients. ScRNA-seq reveals that ERAP2 expression is significantly elevated in patients with sJIA compared to normal and other subtypes, particularly in monocytes. Bulk RNA-seq with ROC analysis demonstrating significant diagnostic power (AUC = 0.86, 95%CI: 0.71-1.00) in discriminating sJIA from healthy controls. Literature and Phe-WAS search revealed that ERAP2 is primarily studied in the context of genetic predisposition to disease and is closely related to autoimmune disorders.

conclusionsERAP2 was identified as a candidate associated with JIA, especially sJIA, through integrative omics analysis, indicating its potential role in protein-mediated disease mechanisms and therapeutic targeting.

Indexed as

AminopeptidasesArthritis, JuvenileProteomeChildFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMendelian Randomization AnalysisMinor Histocompatibility AntigensPolymorphism, Single NucleotideWhole Genome SequencingAminopeptidasesERAP1 protein, humanERAP2 protein, humanMinor Histocompatibility AntigensProteomeIntegrative Omics PipelineJuvenile idiopathic arthritisLiterature reviewPhenome-wide association studyScRNA-seqWhole Genome Sequencing

Identifiers

PMID40898345
PMCPMC12406534

What Socratic holds

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Registered trials

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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 Socratic graph.