Zou Xue-Lun, Wang Sai, Wang Lei-Yun, Xiao Lin-Xiao, Yao Tian-Xing, Zeng Yi, Zhang Le
Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya Hospital, Institute of Clinical Pharmacology, Central South University, Changsha, China.
Front Genet. 2021 Nov 17;12:727475. doi: 10.3389/fgene.2021.727475. eCollection 2021.
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. 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. Genetic evaluations revealed that childhood obesity was associated with a higher risk of stroke (OR = 1.04, 95%CI: 1.01-1.07, = 0.005) and IS (OR = 1.05, 95%CI: 1.02-1.08, = 0.003), but not with intracerebral haemorrhage (ICH, OR = 0.93, 95%CI: 0.80-1.09, = 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, = 0.016) but not with cardioembolic stroke (OR = 1.06, 95%CI: 0.96-1.18, = 0.21) and small vessel stroke (OR = 1.06, 95%CI: 0.98-1.15, = 0.17). These results were stable in the sensitivity analysis and remained significant after Bonferroni correction. 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.
儿童肥胖与中风之间的因果关系仍不明确。我们的目的是通过进行孟德尔随机化(MR)分析,阐明儿童肥胖与中风及其亚型风险之间的因果关系。儿童肥胖的基因工具来自一项对13848名欧洲参与者的全基因组关联研究(GWAS)。使用MEGASTROKE GWAS数据集评估中风、脑出血、缺血性中风(IS)及其亚型的汇总水平数据,该数据集包括446696名欧洲成年人。本MR分析采用逆方差加权、加权中位数分析、MR-Egger回归、MR多效性残差和异常值检验(MR-PRESSO)以及MR稳健调整轮廓得分。进行留一法敏感性检验、MR-PRESSO全局检验和 Cochr an Q检验以确认结果的准确性和稳健性。基因评估显示,儿童肥胖与中风风险较高相关(OR = 1.04,95%CI:1.01 - 1.07,P = 0.005)和IS(OR = 1.05,95%CI:1.02 - 1.08,P = 0.003),但与脑出血(ICH,OR = 0.93,95%CI:0.80 - 1.09,P = 0.39)无关。在亚型分析中,儿童肥胖也与大动脉中风(LAS,OR = 1.12,95%CI:1.02 - 1.22,P = 0.016)相关,但与心源性栓塞性中风(OR = 1.06,95%CI:0.96 - 1.18,P = 0.21)和小血管中风(OR = 1.06,95%CI:0.98 - 1.15,P = 0.17)无关。这些结果在敏感性分析中稳定,经Bonferroni校正后仍具有显著性。我们的研究提供了证据,表明儿童肥胖与中风、IS和LAS风险较高相关。应在儿童肥胖人群中加强对中风,尤其是IS和LAS的预防。