载脂蛋白(a)与动脉僵硬度的关联：一项孟德尔随机化研究。

Association of Lipoprotein(a) with arterial stiffness: A Mendelian randomization study.

机构信息

Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.

School of Biomedical Engineering and Imaging Sciences, Kings College London, London, UK.

出版信息

Eur J Clin Invest. 2024 May;54(5):e14168. doi: 10.1111/eci.14168. Epub 2024 Jan 18.

DOI:10.1111/eci.14168

PMID:38239089

Abstract

BACKGROUND

In this study we used Mendelian randomization (MR) to investigate the potential causal association of lipoprotein (a) [Lp(a)] levels with pulse wave velocity (PWV).

METHODS

Genetic variants associated with Lp(a) were retrieved from the UK Biobank GWAS (N = 290,497). A non- overlapping GWAS based on a European cohort (N = 7,000) was used to obtain genetic associations with PWV (outcome) and utilized two different measures for the same trait, brachial-ankle (baPWV) and carotid-femoral (cfPWV) PWV. We applied a two-sample MR using the inverse variance weighting method (IVW) and a series of sensitivity analyses for 170 SNPs that were selected as instrumental variables (IVs).

RESULTS

Our analyses do not support a causal association between Lp(a) and PWV for neither measurement [β(baPWV) = -.0005, p = .8 and β(cfPWV) = -.006, p = .16]. The above findings were consistent across sensitivity analyses including weighted median, mode-based estimation, MR-Egger regression and MR-PRESSO.

CONCLUSION

We did not find evidence indicating that Lp(a) is causally associated with PWV, the gold standard marker of arterial stiffness.

摘要

背景

本研究采用孟德尔随机化（MR）方法，探讨脂蛋白（a）[Lp(a)]水平与脉搏波速度（PWV）之间潜在的因果关联。

方法

从英国生物银行 GWAS（N=290497）中检索与 Lp(a)相关的遗传变异。利用基于欧洲队列的非重叠 GWAS（N=7000）获得与 PWV（结局）相关的遗传关联，并利用两种不同的方法测量同一特征，即肱踝脉搏波速度（baPWV）和颈股脉搏波速度（cfPWV）。我们应用两样本 MR 方法，采用逆方差加权法（IVW）和一系列敏感性分析，对 170 个被选为工具变量（IVs）的 SNP 进行分析。

结果

我们的分析结果不支持 Lp(a)与 PWV 之间存在因果关系，无论是使用 baPWV 还是 cfPWV 测量[baPWV：β=-0.0005，p=0.8；cfPWV：β=-0.006，p=0.16]。敏感性分析结果包括加权中位数、基于模式的估计、MR-Egger 回归和 MR-PRESSO，结果均一致。