Related Experiment Video
Updated: May 9, 2025
06:08
Ultrasound Imaging of the Thoracic and Abdominal Aorta in Mice to Determine Aneurysm Dimensions
Published on: March 8, 2019
19.1K
Integrative Genome-wide Association Meta-analysis of Aortic Aneurysm and Dissection Identifies Five Novel Genes
Yifan Du1,2, Yunlong Guan1, Zhonghe Shao1
1Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Genomics, Proteomics & Bioinformatics
|April 29, 2025
Summary
This study identified 24 genetic loci, including four novel ones, associated with aortic aneurysm and dissection (AAD). Findings reveal shared genetic factors with cardiovascular diseases and risk factors, offering new therapeutic targets.
Area of Science:
- Genetics
- Cardiovascular Biology
- Genomics
Background:
- Aortic aneurysm and dissection (AAD) is a significant cause of cardiovascular mortality with a strong genetic component.
- Previous genetic studies of AAD subtypes were conducted separately, limiting a comprehensive understanding of shared genetic mechanisms.
Purpose of the Study:
- To conduct a large-scale genome-wide association study (GWAS) meta-analysis combining AAD subtypes to identify novel genetic loci.
- To explore the biological mechanisms and therapeutic targets underlying AAD through gene prioritization and functional validation.
Main Methods:
- Performed a GWAS meta-analysis of 11,148 AAD cases and 708,468 controls of European ancestry.
- Utilized cell type-specific analysis, gene prioritization methods, and ex vivo/in vitro experiments for functional validation.
- Investigated genetic correlations with other cardiovascular diseases and causal associations with risk factors.
Main Results:
- Identified 24 susceptibility loci for AAD, including four novel loci (at 1p21.2, 2p22.2, 6q22.1, and 12q14.3).
- Highlighted arteries as key tissues and implicated elastic fiber formation and TGF-β signaling pathways.
- Confirmed genetic correlations with cardiovascular diseases and causal links with BMI, lipids, and pulse pressure.
- Validated five novel genes (PALMD, CRIM1, FRK, HMGA2, NT5DC1) as regulators of smooth muscle and endothelial cell functions.
Conclusions:
- This study enhances the understanding of the genetic architecture of AAD by integrating its subtypes.
- Findings provide novel insights into AAD pathogenesis, emphasizing shared genetic factors with cardiovascular diseases and risk factors.
- Identified potential therapeutic targets and strategies for AAD treatment.
