Lipoprotein(a) and stroke: a two-sample Mendelian randomization study

Frontiers in Aging Neuroscience

Aging Neuroscience

Yuefei Wu¹  Tianqi Xu¹  Chenhui Zhou²  Yiwen Wu²  Xinpeng Deng²  Xiang Gao²  Jie Sun²  Yi Huang³  Liyuan Han⁴  Ruijie Zhang⁴ 

[1] Department of Neurology, The First Affiliated Hospital of Ningbo University, Ningbo, China;Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Ningbo, China;Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Ningbo, China;Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, China;Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China;Department of Global Health, Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China;

关键词: stroke;    lipoprotein(a);    ischemic stroke;    large-artery atherosclerotic stroke;    Mendelian randomization;   

DOI  :  10.3389/fnagi.2023.1178079

 received in 2023-03-02, accepted in 2023-04-26,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundTo evaluate the causal relationship between lipoprotein(a) Lp(a) and stroke risk.MethodAdopting two grand scale genome-wide association study (GWAS) databases, the instrumental variables were selected on the basis that the genetic loci met the criteria of being independent of each other and closely related to Lp(a). Summary-level data for outcomes, ischemic stroke and its subtypes were acquired from the UK Biobank and MEGASTROKE consortium databases. Two-sample MR analyses were achieved using inverse variance-weighted (IVW) meta-analysis (primary analysis), weighted median analysis, and the MR Egger regression method. Multivariable-adjusted Cox regression models were also used for observational analysis.ResultGenetically predicted Lp(a) was marginally related with higher odds of total stroke (odds ratio (OR) [95% confidence intervals (CI)]: 1.003 [1.001–1.006], p = 0.010), ischemic stroke (OR [95% CI]: 1.004[1.001–1.007], p = 0.004), and large-artery atherosclerotic stroke (OR [95% CI]: 1.012 [1.004–1.019], p = 0.002) when the IVW estimator was used on the MEGASTROKE data. The associations of Lp(a) with stroke and ischemic stroke were also remarkable in the primary analysis using the UK Biobank data. Higher Lp(a) levels were also related with increased total stroke and ischemic stroke risk in the observational research data in the UK Biobank database.ConclusionGenetically predicted higher Lp(a) perhaps rise the risk of total stroke, ischemic stroke, and large-artery atherosclerotic stroke.

【 授权许可】

Unknown   
Copyright © 2023 Huang, Zhang, Han, Wu, Deng, Xu, Wu, Gao, Zhou and Sun.