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

Yi Huang; Ruijie Zhang; Liyuan Han; Yiwen Wu; Xinpeng Deng; Tianqi Xu; Yuefei Wu; Xiang Gao; Chenhui Zhou; Jie Sun

doi:10.3389/fnagi.2023.1178079

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

Front Aging Neurosci. 2023 May 12:15:1178079. doi: 10.3389/fnagi.2023.1178079. eCollection 2023.

Authors

Yi Huang^{1

2}, Ruijie Zhang^{3

4}, Liyuan Han^{3

4}, Yiwen Wu¹, Xinpeng Deng¹, Tianqi Xu⁵, Yuefei Wu⁵, Xiang Gao¹, Chenhui Zhou¹, Jie Sun¹

Affiliations

¹ Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Ningbo, China.
² Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, China.
³ Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China.
⁴ Department of Global Health, Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China.
⁵ Department of Neurology, The First Affiliated Hospital of Ningbo University, Ningbo, China.

Abstract

Background: To evaluate the causal relationship between lipoprotein(a) Lp(a) and stroke risk.

Method: Adopting 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.

Result: Genetically 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.

Conclusion: Genetically predicted higher Lp(a) perhaps rise the risk of total stroke, ischemic stroke, and large-artery atherosclerotic stroke.

Keywords: Mendelian randomization; ischemic stroke; large-artery atherosclerotic stroke; lipoprotein(a); stroke.