Table2_Childhood Obesity and Risk of Stroke: A Mendelian Randomisation Analysis.docx

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.

背景：儿童肥胖与脑卒中之间的因果关联尚未明确。本研究旨在通过孟德尔随机化（Mendelian randomisation, MR）分析，阐明儿童肥胖与脑卒中及其亚型的发病风险之间的因果关联。
方法：儿童肥胖的遗传工具变量来自一项纳入13848名欧洲参与者的全基因组关联研究（genome-wide association study, GWAS）。脑卒中、脑内出血、缺血性脑卒中（ischaemic stroke, IS）及其亚型的汇总级数据，取自包含446696名欧洲成年人的MEGASTROKE GWAS数据集。本MR分析采用了逆方差加权法、加权中位数法、MR-Egger回归、MR多效性残差和异常值检验（MR Pleiotropy RESidual Sum and Outlier test, MR-PRESSO）以及MR稳健调整轮廓得分法。同时通过留一法敏感性检验、MR-PRESSO全局检验以及科克兰Q检验（Cochran’s Q test）验证研究结果的准确性与稳健性。
结果：遗传分析结果显示，儿童肥胖与脑卒中（比值比OR=1.04，95%置信区间CI：1.01~1.07，p=0.005）及缺血性脑卒中（IS，OR=1.05，95%CI：1.02~1.08，p=0.003）的发病风险升高显著相关，但与脑内出血（intracerebral haemorrhage, ICH，OR=0.93，95%CI：0.80~1.09，p=0.39）无显著关联。亚型分析表明，儿童肥胖与大动脉脑卒中（large artery stroke, LAS，OR=1.12，95%CI：1.02~1.22，p=0.016）显著相关，但与心源性脑卒中（OR=1.06，95%CI：0.96~1.18，p=0.21）及小血管脑卒中（OR=1.06，95%CI：0.98~1.15，p=0.17）无显著关联。敏感性分析证实上述结果稳健可靠，经邦费罗尼校正（Bonferroni correction）后仍具有统计学意义。
结论：本研究证实儿童肥胖与脑卒中、缺血性脑卒中及大动脉脑卒中的发病风险升高显著相关。对于合并儿童肥胖的人群，应加强脑卒中的预防工作，尤其需重点防控缺血性脑卒中与大动脉脑卒中。