Department of Clinical Research Center, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Department of Psychiatry, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Int J Stroke. 2022 Feb;17(2):172-179. doi: 10.1177/17474930211006285. Epub 2021 Apr 7.
Observational studies have found an association between visceral adiposity and stroke.
The purpose of this study was to investigate the role and genetic effect of visceral adipose tissue accumulation on stroke and its subtypes.
In this two-sample Mendelian randomization study, genetic variants (221 single nucleotide polymorphisms; P < 5 × 10) using as instrumental variables for Mendelian randomization analysis was obtained from a genome-wide association study of visceral adipose tissue. The outcome datasets for stroke and its subtypes were obtained from the MEGASTROKE consortium (up to 67,162 cases and 453,702 controls). Mendelian randomization standard analysis (inverse variance weighted method) was conducted to investigate the effect of genetic liability to visceral adiposity on stroke and its subtypes. Sensitivity analyses (Mendelian randomization-Egger, weighted median, Mendelian randomization-pleiotropy residual sum and outlier) were also utilized to assess horizontal pleiotropy and remove outliers. Multi-variable Mendelian randomization analysis was employed to adjust potential confounders.
In the standard Mendelian randomization analysis, genetically determined visceral adiposity (per 1 SD) was significantly associated with a higher risk of stroke (odds ratio (OR) 1.30; 95% confidence interval (CI) 1.21-1.41, P = 1.48× 10), ischemic stroke (OR 1.30; 95% CI 1.20-1.41, P = 4.01 × 10) and large artery stroke (OR 1.49; 95% CI 1.22-1.83, P = 1.16 × 10). The significant association was also found in sensitivity analysis and multi-variable Mendelian randomization analysis.
Genetic liability to visceral adiposity was significantly associated with an increased risk of stroke, ischemic stroke, and large artery stroke. The effect of genetic susceptibility to visceral adiposity on the stroke warrants further investigation.
观察性研究发现内脏脂肪与中风之间存在关联。
本研究旨在探讨内脏脂肪组织堆积对中风及其亚型的作用和遗传效应。
在这项两样本孟德尔随机化研究中，使用全基因组关联研究中获得的内脏脂肪的遗传变异（221 个单核苷酸多态性；P < 5×10）作为孟德尔随机化分析的工具变量。中风及其亚型的结果数据集来自 MEGASTROKE 联盟（多达 67,162 例病例和 453,702 例对照）。采用孟德尔随机化标准分析（逆方差加权法）来研究遗传易感性对中风及其亚型的影响。还进行了敏感性分析（孟德尔随机化-Egger、加权中位数、孟德尔随机化-多效性残差和异常值）以评估水平多效性并去除异常值。多变量孟德尔随机化分析用于调整潜在的混杂因素。
在标准孟德尔随机化分析中，遗传决定的内脏脂肪（每 1 个标准差）与中风风险增加显著相关（比值比（OR）1.30；95%置信区间（CI）1.21-1.41，P=1.48×10）、缺血性中风（OR 1.30；95% CI 1.20-1.41，P=4.01×10）和大动脉性中风（OR 1.49；95% CI 1.22-1.83，P=1.16×10）。敏感性分析和多变量孟德尔随机化分析也发现了显著的相关性。
遗传易感性与内脏脂肪与中风、缺血性中风和大动脉性中风的风险增加显著相关。遗传易感性对中风的影响值得进一步研究。
