Abstract:
:Fibroblast growth factor 23 (FGF23), which is involved in the regulation of vitamin D, is an emerging independent risk factor for cardiovascular diseases. Previous studies have demonstrated a positive association between FGF23 and stroke. In this study, we aimed to assess the association of FGF23 with ischemic stroke and its subtypes by applying a Mendelian randomization (MR) framework. Five genetic variants obtained from a genome-wide association study involving 16,624 European subjects were used as valid instruments of circulating FGF23 levels. MR was applied to infer the causality of FGF23 levels and the risk of ischemic stroke using data from the MEGASTROKE consortium. Subsequently, several MR analyses, including inverse-variance weighted meta-analysis, MR-Egger, weighted median estimate (WME), MR Pleiotropy Residual Sum and Outlier were performed. The heterogeneity test analysis, including Cochran's Q, I2 test and leave-one-out analysis were also applied. Furthermore, potential horizontal/vertical pleiotropy was assessed. Lastly, the power of MR analysis was tested. Three validated variants were found to be associated with circulating FGF23 levels and were used for further investigation. We found that high expression level of FGF23 was not associated with any ischemic stroke. However, a causal association between genetically predicted FGF23 levels and the risk of large-artery atherosclerotic stroke (LAS) was significant, with an odds ratio of 1.74 (95% confidence interval = 1.08-2.81) per standard deviation increase in circulating FGF23 levels. Our findings provide support for the causal association between FGF23 and LAS, and therefore, offer potential therapeutic targets for LAS. The specific roles of FGF23 in LAS and associated molecules require further investigation.
journal_name
Front Genetjournal_title
Frontiers in geneticsauthors
Zheng K,Lin L,Cui P,Liu T,Chen L,Yang C,Jiang Wdoi
10.3389/fgene.2020.608517subject
Has Abstractpub_date
2020-12-23 00:00:00pages
608517issn
1664-8021journal_volume
11pub_type
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journal_title:Frontiers in genetics
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pub_type: 杂志文章
doi:10.3389/fgene.2015.00031
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pub_type: 杂志文章
doi:10.3389/fgene.2015.00193
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pub_type: 杂志文章
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journal_title:Frontiers in genetics
pub_type: 已发布勘误
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pub_type: 杂志文章
doi:10.3389/fgene.2014.00351
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pub_type: 杂志文章,评审
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更新日期:2018-08-27 00:00:00
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journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2012.00280
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journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2014.00233
更新日期:2014-08-08 00:00:00
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journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.584678
更新日期:2020-12-03 00:00:00
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pub_type: 杂志文章,评审
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