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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.727475/full |
| _version_ | 1819007111310344192 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-21T00:19:23Z |
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| id | doaj.art-db59a0818cae448a9b78cf3c2d3977e0 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-21T00:19:23Z |
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| spelling | doaj.art-db59a0818cae448a9b78cf3c2d3977e02022-12-21T19:22:08ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-11-011210.3389/fgene.2021.727475727475Childhood Obesity and Risk of Stroke: A Mendelian Randomisation AnalysisXue-Lun Zou0Sai Wang1Lei-Yun Wang2Lin-Xiao Xiao3Tian-Xing Yao4Yi Zeng5Le Zhang6Department of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya Hospital, Institute of Clinical Pharmacology, Central South University, Changsha, ChinaDepartment of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Geriatrics, Second Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaBackground: 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.https://www.frontiersin.org/articles/10.3389/fgene.2021.727475/fullchildhood obesitystrokemendelian randomizationgeneticsGWAS |
| spellingShingle | 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 Frontiers in Genetics childhood obesity stroke mendelian randomization genetics GWAS |
| title | 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_short | Childhood Obesity and Risk of Stroke: A Mendelian Randomisation Analysis |
| title_sort | childhood obesity and risk of stroke a mendelian randomisation analysis |
| topic | childhood obesity stroke mendelian randomization genetics GWAS |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.727475/full |
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