Evidence map›Paper›PMID 39267096›Full record

ArticleCardiovascular diabetology2024

Identification of potential therapeutic targets for nonischemic cardiomyopathy in European ancestry: an integrated multiomics analysis.

Kaijia Shi, Xu Chen, Yangyang Zhao, Peihu Li, Jinxuan Chai, Jianmin Qiu, Zhihua Shen, Junli Guo, Wei Jie

Abstract read
In one paragraph

Article in Cardiovascular diabetology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Risk factors of clonal hematopoiesis of indeterminate potential.Clinical medicine (London, England) · 2026
    Article
  2. Observational
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. LILRA5Frontiers in cellular and infection microbiology · 2025
    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

9 authors.

Kaijia Shi *Key Laboratory of Tropical Translational Medicine of Ministry of Education & Key Laboratory for Tropical Cardiovascular Diseases Research of Hainan Province, School of Public Health, Hainan Medical University, Haikou, 571199, China.ORCID 0000-0001-9286-2879
Xu Chen *Department of Intensive Care Unit, Yuhuangding Hospital, Yantai, 264000, China.ORCID 0009-0007-3354-6578
Yangyang ZhaoKey Laboratory of Tropical Translational Medicine of Ministry of Education & Key Laboratory for Tropical Cardiovascular Diseases Research of Hainan Province, School of Public Health, Hainan Medical University, Haikou, 571199, China.
Peihu LiKey Laboratory of Tropical Translational Medicine of Ministry of Education & Key Laboratory for Tropical Cardiovascular Diseases Research of Hainan Province, School of Public Health, Hainan Medical University, Haikou, 571199, China.
Jinxuan ChaiKey Laboratory of Tropical Translational Medicine of Ministry of Education & Key Laboratory for Tropical Cardiovascular Diseases Research of Hainan Province, School of Public Health, Hainan Medical University, Haikou, 571199, China.
Jianmin QiuKey Laboratory of Tropical Translational Medicine of Ministry of Education & Key Laboratory for Tropical Cardiovascular Diseases Research of Hainan Province, School of Public Health, Hainan Medical University, Haikou, 571199, China.
Zhihua ShenDepartment of Pathology and Pathophysiology, School of Basic Medicine Sciences, Guangdong Medical University, Zhanjiang, 524023, China. shenzh@gdmu.edu.cn.ORCID 0000-0002-0451-8873
Junli GuoKey Laboratory of Tropical Translational Medicine of Ministry of Education & Key Laboratory for Tropical Cardiovascular Diseases Research of Hainan Province, School of Public Health, Hainan Medical University, Haikou, 571199, China. guojl@muhn.edu.cn.ORCID 0000-0002-9740-9819
Wei JieKey Laboratory of Tropical Translational Medicine of Ministry of Education & Key Laboratory for Tropical Cardiovascular Diseases Research of Hainan Province, School of Public Health, Hainan Medical University, Haikou, 571199, China. wei_jie@muhn.edu.cn.ORCID 0000-0002-1869-1458

Funding

Hainan Key Research and Development Project ZDYF2020122, ZDYF2022SHFZ038Innovative Research Projects for Graduate Students in Hainan Province Qhyb2022-140National Natural Science Foundation of China 82060053, 82260083National Natural Science Foundation of China U220A20270the Innovational Fund for Scientific and Technological Personnel of Hainan Province KJRC2023B07
6 · The paper itself

Abstract

backgroundNonischemic cardiomyopathy (NISCM) is a clinical challenge with limited therapeutic targets. This study aims to identify promising drug targets for NISCM.

methodsWe utilized cis-pQTLs from the deCODE study, which includes data from 35,559 Icelanders, and SNPs from the FinnGen study, which includes data from 1,754 NISCM cases and 340,815 controls of Finnish ancestry. Mendelian randomization (MR) analysis was performed to estimate the causal relationship between circulating plasma protein levels and NISCM risk. Proteins with significant associations underwent false discovery rate (FDR) correction, followed by Bayesian colocalization analysis. The expression of top two proteins, LILRA5 and NELL1, was further analyzed using various NISCM datasets. Descriptions from the Human Protein Atlas (HPA) validated protein expression. The impact of environmental exposures on LILRA5 was assessed using the Comparative Toxicogenomics Database (CTD), and molecular docking identified the potential small molecule interactions.

resultsMR analysis identified 255 circulating plasma proteins associated with NISCM, with 16 remaining significant after FDR correction. Bayesian colocalization analysis identified LILRA5 and NELL1 as significant, with PP.H4 > 0.8. LILRA5 has a protective effect (OR = 0.758, 95% CI, 0.670-0.857) while NELL1 displays the risk effect (OR = 1.290, 95% CI, 1.199-1.387) in NISCM. Decreased LILRA5 expression was found in NISCM such as diabetic, hypertrophic, dilated, and inflammatory cardiomyopathy, while NELL1 expression increased in hypertrophic cardiomyopathy. HPA data indicated high LILRA5 expression in neutrophils, macrophages and endothelial cells within normal heart and limited NELL1 expression. Immune infiltration analysis revealed decreased neutrophil in diabetic cardiomyopathy. CTD analysis identified several small molecules that affect LILRA5 mRNA expression. Among these, Estradiol, Estradiol-3-benzoate, Gadodiamide, Topotecan, and Testosterone were found to stably bind to the LILRA5 protein at the conserved VAL-15 or THR-133 residues in the Ig-like C2 domain.

conclusionBased on European Ancestry Cohort, this study reveals that LILRA5 and NELL1 are potential therapeutic targets for NISCM, with LILRA5 showing particularly promising prospects in diabetic cardiomyopathy. Several small molecules interact with LILRA5, implying potential clinical implication.

Indexed as

Calcium-Binding ProteinsCardiomyopathiesGenetic Predisposition to DiseaseNerve Tissue ProteinsPolymorphism, Single NucleotideWhite PeopleBayes TheoremCase-Control StudiesFemaleGene-Environment InteractionHumansIcelandMaleMiddle AgedMolecular Docking SimulationMolecular Targeted TherapyCalcium-Binding ProteinsNELL1 protein, humanNerve Tissue ProteinsCis-pQTLMendelian randomizationMolecular dockingMultiomicsNonischemic cardiomyopathyTherapeutic targets

Identifiers

PMID39267096
PMCPMC11396958

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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 OpenQuestion graph.