Genetic insights into therapeutic targets for aortic aneurysms: A Mendelian randomization study

主动脉瘤治疗靶点的遗传学见解:孟德尔随机化研究

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作者:Yanghui Chen, Xin Xu, Linlin Wang, Ke Li, Yang Sun, Lei Xiao, Jiaqi Dai, Man Huang, Yan Wang, Dao Wen Wang

Background

As aortic aneurysms (AAs) enlarge, they can become life-threatening if left undiagnosed or neglected. At present, there is a lack of radical treatments for preventing disease progression. Therefore, we aimed to identify effective drug targets that slow the progression of AAs.

Methods

A Mendelian randomization (MR) analysis was conducted to identify therapeutic targets which are associated with AAs. Summary statistics for AAs were obtained from two datasets: the UK Biobank (2228 cases and 408,565 controls) and the FinnGen study (3658 cases and 244,907 controls). Cis-expression quantitative trait loci (cis-eQTL) for druggable genes were retrieved from the eQTLGen Consortium and used as genetic instrumental variables. Colocalization analysis was performed to determine the probability that single nucleotide polymorphisms (SNPs) associated with AAs and eQTL shared causal genetic variants. Findings: Four drug targets (BTN3A1, FASN, PLAU, and PSMA4) showed significant MR

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