Childhood Obesity and Risk of Stroke: A Mendelian Randomisation Analysis

Background: The causal relationship between childhood obesity and stroke remains unclear. Our objective was to elucidate the causal relationship between childhood obesity and the risk of stroke and its subtypes by performing Mendelian randomisation (MR) analyses.Methods: Genetic instruments for chil...

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Autores principales:	Xue-Lun Zou, Sai Wang, Lei-Yun Wang, Lin-Xiao Xiao, Tian-Xing Yao, Yi Zeng, Le Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	childhood obesity stroke mendelian randomization genetics GWAS Genetics QH426-470
Acceso en línea:	https://doaj.org/article/db59a0818cae448a9b78cf3c2d3977e0
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spelling	oai:doaj.org-article:db59a0818cae448a9b78cf3c2d3977e02021-11-17T11:32:20ZChildhood Obesity and Risk of Stroke: A Mendelian Randomisation Analysis1664-802110.3389/fgene.2021.727475https://doaj.org/article/db59a0818cae448a9b78cf3c2d3977e02021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.727475/fullhttps://doaj.org/toc/1664-8021Background: The causal relationship between childhood obesity and stroke remains unclear. Our objective was to elucidate the causal relationship between childhood obesity and the risk of stroke and its subtypes by performing Mendelian randomisation (MR) analyses.Methods: Genetic instruments for childhood obesity were obtained from a genome-wide association study (GWAS) of 13,848 European participants. Summary level data for stroke, intracerebral haemorrhage, ischaemic stroke (IS), and its subtypes were evaluated using the MEGASTROKE GWAS dataset, which included 446,696 European adults. Inverse-variance weighting, weighted-median analysis, MR-Egger regression, MR Pleiotropy RESidual Sum and Outlier test (MR-PRESSO), and MR-Robust Adjusted Profile Score were applied in this MR analysis. The leave-one-out sensitivity test, MR-PRESSO Global test, and Cochran’s Q test were conducted to confirm the accuracy and robustness of our results.Results: Genetic evaluations revealed that childhood obesity was associated with a higher risk of stroke (OR = 1.04, 95%CI: 1.01–1.07, p = 0.005) and IS (OR = 1.05, 95%CI: 1.02–1.08, p = 0.003), but not with intracerebral haemorrhage (ICH, OR = 0.93, 95%CI: 0.80–1.09, p = 0.39). In the subtype analysis, childhood obesity was also associated with large artery stroke (LAS, OR = 1.12, 95%CI: 1.02–1.22, p = 0.016) but not with cardioembolic stroke (OR = 1.06, 95%CI: 0.96–1.18, p = 0.21) and small vessel stroke (OR = 1.06, 95%CI: 0.98–1.15, p = 0.17). These results were stable in the sensitivity analysis and remained significant after Bonferroni correction.Conclusion: Our study provides evidence that childhood obesity is associated with a higher risk of stroke, IS, and LAS. The prevention of stroke, especially IS and LAS, should be promoted in populations with childhood obesity.Xue-Lun ZouSai WangLei-Yun WangLin-Xiao XiaoTian-Xing YaoYi ZengLe ZhangFrontiers Media S.A.articlechildhood obesitystrokemendelian randomizationgeneticsGWASGeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	childhood obesity stroke mendelian randomization genetics GWAS Genetics QH426-470
spellingShingle	childhood obesity stroke mendelian randomization genetics GWAS Genetics QH426-470 Xue-Lun Zou Sai Wang Lei-Yun Wang Lin-Xiao Xiao Tian-Xing Yao Yi Zeng Le Zhang Childhood Obesity and Risk of Stroke: A Mendelian Randomisation Analysis
description	Background: The causal relationship between childhood obesity and stroke remains unclear. Our objective was to elucidate the causal relationship between childhood obesity and the risk of stroke and its subtypes by performing Mendelian randomisation (MR) analyses.Methods: Genetic instruments for childhood obesity were obtained from a genome-wide association study (GWAS) of 13,848 European participants. Summary level data for stroke, intracerebral haemorrhage, ischaemic stroke (IS), and its subtypes were evaluated using the MEGASTROKE GWAS dataset, which included 446,696 European adults. Inverse-variance weighting, weighted-median analysis, MR-Egger regression, MR Pleiotropy RESidual Sum and Outlier test (MR-PRESSO), and MR-Robust Adjusted Profile Score were applied in this MR analysis. The leave-one-out sensitivity test, MR-PRESSO Global test, and Cochran’s Q test were conducted to confirm the accuracy and robustness of our results.Results: Genetic evaluations revealed that childhood obesity was associated with a higher risk of stroke (OR = 1.04, 95%CI: 1.01–1.07, p = 0.005) and IS (OR = 1.05, 95%CI: 1.02–1.08, p = 0.003), but not with intracerebral haemorrhage (ICH, OR = 0.93, 95%CI: 0.80–1.09, p = 0.39). In the subtype analysis, childhood obesity was also associated with large artery stroke (LAS, OR = 1.12, 95%CI: 1.02–1.22, p = 0.016) but not with cardioembolic stroke (OR = 1.06, 95%CI: 0.96–1.18, p = 0.21) and small vessel stroke (OR = 1.06, 95%CI: 0.98–1.15, p = 0.17). These results were stable in the sensitivity analysis and remained significant after Bonferroni correction.Conclusion: Our study provides evidence that childhood obesity is associated with a higher risk of stroke, IS, and LAS. The prevention of stroke, especially IS and LAS, should be promoted in populations with childhood obesity.
format	article
author	Xue-Lun Zou Sai Wang Lei-Yun Wang Lin-Xiao Xiao Tian-Xing Yao Yi Zeng Le Zhang
author_facet	Xue-Lun Zou Sai Wang Lei-Yun Wang Lin-Xiao Xiao Tian-Xing Yao Yi Zeng Le Zhang
author_sort	Xue-Lun Zou
title	Childhood Obesity and Risk of Stroke: A Mendelian Randomisation Analysis
title_short	Childhood Obesity and Risk of Stroke: A Mendelian Randomisation Analysis
title_full	Childhood Obesity and Risk of Stroke: A Mendelian Randomisation Analysis
title_fullStr	Childhood Obesity and Risk of Stroke: A Mendelian Randomisation Analysis
title_full_unstemmed	Childhood Obesity and Risk of Stroke: A Mendelian Randomisation Analysis
title_sort	childhood obesity and risk of stroke: a mendelian randomisation analysis
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/db59a0818cae448a9b78cf3c2d3977e0
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_version_	1718425640089157632

Childhood Obesity and Risk of Stroke: A Mendelian Randomisation Analysis

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