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

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 oth...

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Autores principales: Huang, Yi, Zhang, Ruijie, Han, Liyuan, Wu, Yiwen, Deng, Xinpeng, Xu, Tianqi, Wu, Yuefei, Gao, Xiang, Zhou, Chenhui, Sun, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10213338/
https://www.ncbi.nlm.nih.gov/pubmed/37251802
http://dx.doi.org/10.3389/fnagi.2023.1178079
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author Huang, Yi
Zhang, Ruijie
Han, Liyuan
Wu, Yiwen
Deng, Xinpeng
Xu, Tianqi
Wu, Yuefei
Gao, Xiang
Zhou, Chenhui
Sun, Jie
author_facet Huang, Yi
Zhang, Ruijie
Han, Liyuan
Wu, Yiwen
Deng, Xinpeng
Xu, Tianqi
Wu, Yuefei
Gao, Xiang
Zhou, Chenhui
Sun, Jie
author_sort Huang, Yi
collection PubMed
description 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.
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spelling pubmed-102133382023-05-27 Lipoprotein(a) and stroke: a two-sample Mendelian randomization study Huang, Yi Zhang, Ruijie Han, Liyuan Wu, Yiwen Deng, Xinpeng Xu, Tianqi Wu, Yuefei Gao, Xiang Zhou, Chenhui Sun, Jie Front Aging Neurosci Aging Neuroscience 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. Frontiers Media S.A. 2023-05-12 /pmc/articles/PMC10213338/ /pubmed/37251802 http://dx.doi.org/10.3389/fnagi.2023.1178079 Text en Copyright © 2023 Huang, Zhang, Han, Wu, Deng, Xu, Wu, Gao, Zhou and Sun. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Aging Neuroscience
Huang, Yi
Zhang, Ruijie
Han, Liyuan
Wu, Yiwen
Deng, Xinpeng
Xu, Tianqi
Wu, Yuefei
Gao, Xiang
Zhou, Chenhui
Sun, Jie
Lipoprotein(a) and stroke: a two-sample Mendelian randomization study
title Lipoprotein(a) and stroke: a two-sample Mendelian randomization study
title_full Lipoprotein(a) and stroke: a two-sample Mendelian randomization study
title_fullStr Lipoprotein(a) and stroke: a two-sample Mendelian randomization study
title_full_unstemmed Lipoprotein(a) and stroke: a two-sample Mendelian randomization study
title_short Lipoprotein(a) and stroke: a two-sample Mendelian randomization study
title_sort lipoprotein(a) and stroke: a two-sample mendelian randomization study
topic Aging Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10213338/
https://www.ncbi.nlm.nih.gov/pubmed/37251802
http://dx.doi.org/10.3389/fnagi.2023.1178079
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