Related Experiment Video
Updated: Jun 7, 2025
Identifying Coronary Artery Calcification on Non-gated Computed Tomography Scans
Published on: August 28, 2018
Systematic identification of therapeutic targets for coronary artery calcification: an integrated transcriptomic and
Lihong Chen1,2, Xiaoqi Ye1,2, Yan Li1,2
1Department of Endocrinology & Metabolism, West China Hospital, Sichuan University, Chengdu, China.
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.
Insights
Coronary artery calcification (CAC) poses significant health risks, but effective treatments are lacking. This study used Mendelian randomization to identify 23 potential therapeutic targets for CAC, including ULK3, DOT1L, and AMH for drug repurposing.
Area of Science:
- Cardiovascular Genetics
- Pharmacogenomics
- Biostatistics
Background:
- Coronary artery calcification (CAC) is a strong predictor of mortality and cardiovascular events.
- Current therapeutic options for treating CAC are limited, highlighting the need for novel treatment strategies.
- Identifying effective therapeutic targets is crucial for developing new treatments for CAC.
Purpose of the Study:
- To identify potential therapeutic targets for Coronary Artery Calcification (CAC) using Mendelian randomization (MR) and colocalization analysis.
- To explore novel drug repurposing opportunities for CAC treatment.
- To leverage genetic and proteomic data for target identification in cardiovascular disease.
Main Methods:
- Utilized expression quantitative trait loci (eQTLs) and protein quantitative trait loci (pQTLs) as genetic instruments.
- Performed Genome-Wide Association Study (GWAS) meta-analysis on 26,909 individuals for CAC associations.
- Applied Mendelian randomization (MR) and colocalization analyses to identify and validate potential therapeutic targets.
Main Results:
- Transcriptomic MR analysis identified 671 genes associated with CAC risk (FDR <0.05).
- Proteomic MR analysis revealed 15 genes significantly associated with CAC.
- Colocalization analysis confirmed associations for CWF19L2, JARID2, MANBA (positive) and KLB (inverse) with CAC risk, identifying 23 potential therapeutic targets overall.
Conclusions:
- Integrated MR analysis of transcriptomic and proteomic data identified multiple potential drug targets for CAC treatment.
- ULK3, DOT1L, and AMH emerged as novel targets for drug repurposing in CAC.
- These findings warrant further investigation for developing new therapeutic strategies for CAC.
More Related Videos
09:06Quantitative Analysis of Cellular Composition in Advanced Atherosclerotic Lesions of Smooth Muscle Cell Lineage-Tracing Mice
Published on: February 20, 2019
10:03Coronary Progenitor Cells and Soluble Biomarkers in Cardiovascular Prognosis after Coronary Angioplasty
Published on: January 28, 2020
