Huang Yunying, Liu Yaozhong, Ma Yingxu, Tu Tao, Liu Na, Bai Fan, Xiao Yichao, Liu Chan, Hu Zhengang, Lin Qiuzhen, Li Mohan, Ning Zuodong, Zhou Yong, Mao Xiquan, Liu Qiming
Department of Cardiovascular Medicine, Second Xiangya Hospital, Central South University, Changsha, China.
Department of Cardiovascular Surgery, Second Xiangya Hospital, Central South University, Changsha, China.
Front Cell Dev Biol. 2022 Feb 3;10:840866. doi: 10.3389/fcell.2022.840866. eCollection 2022.
To evaluate the genetic associations of visceral adipose tissue (VAT) mass with metabolic risk factors and cardiovascular disease (CVD) endpoints and to construct a network analysis about the underlying mechanism using Mendelian randomization (MR) analysis. Using summary statistics from genome-wide association studies (GWAS), we conducted the two-sample MR to assess the effects of VAT mass on 10 metabolic risk factors and 53 CVD endpoints. Genetically predicted VAT mass was associated with metabolic risk factors, including triglyceride (odds ratio, OR, 1.263 [95% confidence interval, CI, 1.203-1.326]), high-density lipoprotein cholesterol (OR, 0.719 [95% CI, 0.678-0.763]), type 2 diabetes (OR, 2.397 [95% CI, 1.965-2.923]), fasting glucose (OR, 1.079 [95% CI, 1.046-1.113]), fasting insulin (OR, 1.194 [95% CI, 1.16-1.229]), and insulin resistance (OR, 1.204 [95% CI, 1.16-1.25]). Genetically predicted VAT mass was associated with CVD endpoints, including atrial fibrillation (OR, 1.414 [95% CI, 1.332 = 1.5]), coronary artery disease (OR, 1.573 [95% CI, 1.439 = 1.72]), myocardial infarction (OR, 1.633 [95% CI, 1.484 =1.796]), heart failure (OR, 1.711 [95% CI, 1.599-1.832]), any stroke (OR, 1.29 [1.193-1.394]), ischemic stroke (OR, 1.292 [1.189-1.404]), large artery stroke (OR, 1.483 [1.206-1.823]), cardioembolic stroke (OR, 1.261 [1.096-1.452]), and intracranial aneurysm (OR, 1.475 [1.235-1.762]). In the FinnGen study, the relevance of VAT mass to coronary heart disease, stroke, cardiac arrhythmia, vascular diseases, hypertensive heart disease, and cardiac death was found. In network analysis to identify the underlying mechanism between VAT and CVDs, VAT mass was positively associated with 23 cardiovascular-related proteins (e.g., Leptin, Hepatocyte growth factor, interleukin-16), and inversely with 6 proteins (e.g., Galanin peptides, Endothelial cell-specific molecule 1). These proteins were further associated with 32 CVD outcomes. Mendelian randomization analysis has shown that VAT mass was associated with a wide range of CVD outcomes including coronary heart disease, cardiac arrhythmia, vascular diseases, and stroke. A few circulating proteins may be the mediators between VAT and CVDs.
评估内脏脂肪组织（VAT）质量与代谢危险因素及心血管疾病（CVD）终点之间的遗传关联，并使用孟德尔随机化（MR）分析构建关于潜在机制的网络分析。利用全基因组关联研究（GWAS）的汇总统计数据，我们进行了两样本MR分析，以评估VAT质量对10种代谢危险因素和53种CVD终点的影响。遗传预测的VAT质量与代谢危险因素相关，包括甘油三酯（优势比，OR，1.263 [95%置信区间，CI，1.203 - 1.326]）、高密度脂蛋白胆固醇（OR，0.719 [95% CI，0.678 - 0.763]）、2型糖尿病（OR，2.397 [95% CI，1.965 - 2.923]）、空腹血糖（OR，1.079 [95% CI，1.046 - 1.113]）、空腹胰岛素（OR，1.194 [95% CI，1.16 - 1.229]）和胰岛素抵抗（OR，1.204 [95% CI，1.16 - 1.25]）。遗传预测的VAT质量与CVD终点相关，包括心房颤动（OR，1.414 [95% CI，1.332 = 1.5]）、冠状动脉疾病（OR，1.573 [95% CI，1.439 = 1.72]）、心肌梗死（OR，1.633 [95% CI，1.484 = 1.796]）、心力衰竭（OR，1.711 [95% CI，1.599 - 1.832]）、任何中风（OR，1.29 [1.193 - 1.394]）、缺血性中风（OR，1.292 [1.189 - 1.404]）、大动脉中风（OR，1.483 [1.206 - 1.823]）、心源性栓塞性中风（OR，1.261 [1.096 - 1.452]）和颅内动脉瘤（OR，1.475 [1.235 - 1.762]）。在芬兰基因研究中，发现VAT质量与冠心病、中风、心律失常、血管疾病、高血压性心脏病和心源性死亡相关。在识别VAT与CVD之间潜在机制的网络分析中，VAT质量与23种心血管相关蛋白（如瘦素、肝细胞生长因子、白细胞介素 - 16）呈正相关，与6种蛋白（如甘丙肽、内皮细胞特异性分子1）呈负相关。这些蛋白进一步与32种CVD结局相关。孟德尔随机化分析表明，VAT质量与包括冠心病、心律失常、血管疾病和中风在内的广泛CVD结局相关。一些循环蛋白可能是VAT与CVD之间的中介物。
