Genetic Dissection of Aortic Aneurysms: Identifying Causal Variants and Novel Druggable Targets Through Mendelian Randomization and Multi-Omics Approaches

DOI:10.4121/8f063c68-fc50-48bf-9a68-367404b6d7ef.v1
The DOI displayed above is for this specific version of this dataset, which is currently the latest. Newer versions may be published in the future. For a link that will always point to the latest version, please use
DOI: 10.4121/8f063c68-fc50-48bf-9a68-367404b6d7ef

Datacite citation style

Dong, Sisi Dong; Zhang, Xiaoxu; DU, Boyao; Shi, Feng; Uzokov, Jamol et. al. (2025): Genetic Dissection of Aortic Aneurysms: Identifying Causal Variants and Novel Druggable Targets Through Mendelian Randomization and Multi-Omics Approaches. Version 1. 4TU.ResearchData. dataset. https://doi.org/10.4121/8f063c68-fc50-48bf-9a68-367404b6d7ef.v1
Other citation styles (APA, Harvard, MLA, Vancouver, Chicago, IEEE) available at Datacite

Dataset

Objective: To identify and validate potential therapeutic genes for abdominal aortic aneurysm (AAA), aortic aneurysm (AA), and thoracic aortic aneurysm (TAA) using genetic and genomic approaches.

Methods: An integrative strategy was applied, including Mendelian randomization (MR), summary-data-based MR (SMR), Bayesian co-localization (eQTLGen, UKB-PPP), and HEIDI tests. Druggable genes were intersected with cis-eQTLs/pQTL data to identify targets, followed by MR analysis using FinnGen and UK Biobank cohorts. Robustness was ensured via reverse causality, heterogeneity, and pleiotropy tests. Multivariate MR, LDSC, PheWAS, and drug prediction analyses were also performed.

Results: MR and validation analyses identified VIPR1, AGRP, LPL, and PROCR as key genes significantly associated with aortic aneurysm risk. These genes showed consistent associations across discovery and replication cohorts, with no significant heterogeneity or horizontal pleiotropy. SMR and HEIDI tests confirmed their causal links, supported by colocalization analysis. PheWAS and drug prediction further highlighted their potential as therapeutic targets, with evidence of specific roles in aneurysm pathogenesis.

Conclusions: This study elucidates the genetic architecture of aortic aneurysms and identifies novel drug targets, facilitating precision medicine for these conditions.

History

  • 2025-08-13 first online, published, posted

Publisher

4TU.ResearchData

Funding

  • (grant code 2023-MS-096) Natural Science Foundation of Liaoning Province
  • (grant code No. DUT22YG107) Fundamental Research Funds for the Central Universities
  • (grant code No.2018M640270) China Postdoctoral Science Foundation
  • (grant code No. 81970402 and 82170507) National Natural Science Foundation of China

Organizations

Dalian University of Technology, School of Chemical Engineering, Ocean Technology and Life Science

DATA

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