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

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

Yi Huang  1   2 , Ruijie Zhang  3   4 , Liyuan Han  3   4 , Yiwen Wu  1 , Xinpeng Deng  1 , Tianqi Xu  5 , Yuefei Wu  5 , Xiang Gao  1 , Chenhui Zhou  1 , Jie Sun  1
Affiliations

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

Yi Huang et al. Front Aging Neurosci. .

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.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
MR results for single instrument variable of Lp(a) on stroke and subtypes in MEGASTROKE.
Figure 2
Figure 2
The sensitive analysis of Lp(a) on stroke in UK-biobank by MR.
Figure 3
Figure 3
The Mendelian randomization (MR) leave-one-out sensitivity analysis for “exposure” on stroke and subtypes. (A) Stroke; (B) Ischemic stroke; (C) Large artery atherosclerosis; (D) Cardioembolic.
See this image and copyright information in PMC

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