Association Between Plasma Proteins and Coronary Atherosclerosis:a Mendelian Randomization Study
10.3969/j.issn.1000-3614.2025.08.011
- VernacularTitle:基于孟德尔随机化的血浆蛋白与冠状动脉粥样硬化的关联研究
- Author:
Jiahe WANG
1
;
Xiaoyu ZHAO
;
Yanchen ZHAO
;
Yunfei LI
;
Yueruijing LIU
;
Jinqi WANG
;
Zhiyuan WU
;
Lixin TAO
Author Information
1. 首都医科大学公共卫生学院 流行病与卫生统计学系,北京 100069
- Publication Type:Journal Article
- Keywords:
coronary atherosclerosis;
plasma proteome;
Mendelian randomization;
causal association
- From:
Chinese Circulation Journal
2025;40(8):799-805
- CountryChina
- Language:Chinese
-
Abstract:
Objectives:To analyze whether there is a causal relationship between plasma proteins and the risk of coronary atherosclerosis(CAS)based on a two-sample Mendelian randomization(MR)analysis and to identify potential therapeutic targets for CAS.Methods:Single nucleotide polymorphisms(SNP)associated with plasma proteins from the UK Biobank Pharmacoproteomics Program(UKB-PPP)database were used as instrumental variables and outcome data were obtained from genome-wide association study databases.The Wald ratio method and inverse variance weighted(IVW)method in two-sample MR were employed as the primary approaches to assess the causal relationship between plasma proteins and CAS.Colocalization analysis was conducted as a sensitivity analysis to ensure the robustness of the MR findings.Results:A total of 132 plasma proteins were found to have causal associations with an increased risk of CAS.Colocalization analysis revealed that 12 plasma proteins shared genetic variants with CAS.Among them,Proprotein convertase subtilise/kexin type 9(PCSK9)(OR=1.23,95%CI:1.15-1.32,P<0.01)and neurocan(NCAN)(OR=1.35,95%CI:1.21-1.52,P<0.01)exhibited posterior probability of hypothesis4(PPH4)values<0.80 in the colocalization analysis,indicating strong support for colocalization and suggesting their potential as primary plasma protein drug targets for CAS.Conclusions:PCSK9 is associated with an increased risk of CAS and is confirmed as a therapeutic target for CAS.NCAN emerges as another potential therapeutic target for CAS.
