Evidence map›Paper›PMID 39526184›Full record

ArticleFrontiers in cardiovascular medicine2024

Systematic identification of therapeutic targets for coronary artery calcification: an integrated transcriptomic and proteomic Mendelian randomization.

Lihong Chen, Xiaoqi Ye, Yan Li, Xingwu Ran

Abstract read
In one paragraph

Article in Frontiers in cardiovascular medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
–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 synthesis or guideline pooled it.

  1. Pooled it
  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.

Lihong Chen *Department of Endocrinology & Metabolism, West China Hospital, Sichuan University, Chengdu, China.
Xiaoqi Ye *Department of Endocrinology & Metabolism, West China Hospital, Sichuan University, Chengdu, China.
Yan LiDepartment of Endocrinology & Metabolism, West China Hospital, Sichuan University, Chengdu, China.
Xingwu RanDepartment of Endocrinology & Metabolism, West China Hospital, Sichuan University, Chengdu, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Coronary artery calcification (CAC) is associated with an increased risk of mortality and cardiovascular events. However, none therapeutic drugs have been proven effective for CAC treatment. The objective of this study was to identify potential therapeutic targets for CAC through the utilization of Mendelian randomization (MR) and colocalization analysis. Methods: The expression quantitative trait loci (eQTLs) of 16,943 genes from the eQTLGen consortium and protein quantitative trait loci (pQTLs) of 4,412 proteins from a plasma proteome were utilized as genetic instruments. Genetic associations with CAC were derived from a GWAS meta-analysis of 26,909 individuals. The MR and colocalization analysis were utilized to identify potential target genes. Results: A total of 671 genes were found to be significantly associated with the risk of CAC based on transcriptomic MR analysis at a false discovery rate <0.05, while proteomic MR analysis identified 15 genes with significant associations with CAC at the same threshold. With robust evidence from colocalization analysis, we observed positive associations between CWF19L2, JARID2, and MANBA and the risk of CAC, while KLB exhibited an inverse association. In summary, our study identified 23 potential therapeutic targets for CAC. Further downstream analysis revealed IGFBP3, ABCC6, ULK3, DOT1L, KLB and AMH as promising candidates for repurposing in the treatment of CAC. Conclusion: The integrated MR analysis of transcriptomic and proteomic data identified multiple potential drug targets for the treatment of CAC. ULK3, DOT1L, and AMH were recognized as novel targets for drug repurposing for CAC and deserve further investigation.

Indexed as

coronary artery calcificationgenetic epidemiological studyMendelian randomizationtarget identificationvascular calcification

Identifiers

PMID39526184
PMCPMC11543530

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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.