A mendelian randomization (MR) study provides causal evidence for the genetic association of lipid metabolism with aortic aneurysms. By using expression quantitative trait loci (eQTLs) related to drug-target genes and SNPs (single nucleotide polymorphisms) located near or within the drug-target loci associated with low-density lipoprotein cholesterol (LDL-C) as proxies for lipid-lowering medications, the drug-target MR study is used to determine the causal association between lipid-lowering drugs and different types of aortic aneurysms (AA). Higher expression of HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) was associated with increased risk of AA (OR = 1.58) and larger lumen size (aortic maximum area: OR = 1.28; aortic minimum area: OR = 1.26). PCSK9 (Proprotein convertase subtilisin/kexin type 9) and CETP (Cholesteryl ester transfer protein) show a suggestive relationship with AA (PCSK9: OR = 1.34; CETP: OR = 1.38). No evidence to support genetically mediated Niemann-Pick C1-Like 1 and LDL-C receptor are associated with AA. The study provides causal evidence that higher gene expression of HMGCR, PCSK9, and CETP increases AA risk, and suggests that corresponding lipid-lowering drugs may be used for preventing arterial aneurysms in high-risk individuals. Source: https://academic.oup.com/
