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Genetically predicted body composition in relation to cardiometabolic traits: a Mendelian randomization study
European Journal of Epidemiology ( IF 13.6 ) Pub Date : 2021-06-30 , DOI: 10.1007/s10654-021-00779-9
Hailuan Zeng 1 , Chenhao Lin 2 , Sijia Wang 3, 4 , Yan Zheng 2 , Xin Gao 1
Affiliation  

Fat mass and fat-free mass are found to be associated with different health outcomes in observational studies, but the underlying causality remains unclear. We aimed to investigate the causal relationships between body composition and cardiometabolic traits using a two-sample Mendelian randomization (MR) approach. Independent genetic variants associated with body fat mass, fat-free mass, and fat percentage in UK Biobank population were used as genetic instrumental variables, and their causal effects on circulatory diseases, type 2 diabetes, glycemic traits, and lipid fractions were estimated from large-scale genome-wide association studies (GWAS) in European populations. Univariable, multivariable, and bidirectional MR analyses were performed. Genetically predicted high fat mass and fat percentage significantly increased risks of most cardiometabolic diseases, and high fat-free mass had protective effects on most cardiometabolic diseases after accounting for fat mass. Fat mass, fat-free mass, and fat percentage were all positively associated with higher risks of atrial fibrillation and flutter, varicose veins, and deep vein thrombosis and pulmonary embolism. High fat mass increased fasting glucose, homeostasis model assessment-insulin resistance (HOMA-IR), triglycerides, decreased high-density lipoprotein cholesterol, and high fat-free mass reduced HOMA-IR, triglycerides, and low-density lipoprotein cholesterol. Genetically predicted fat-free mass was bidirectionally negatively associated with 2-h glucose and total cholesterol. The findings may be helpful in risk stratification and tailoring management of body composition in patients with different cardiometabolic statuses.



中文翻译:

与心脏代谢特征相关的遗传预测身体成分:孟德尔随机化研究

在观察性研究中发现脂肪量和无脂肪量与不同的健康结果相关,但潜在的因果关系尚不清楚。我们旨在使用两样本孟德尔随机化 (MR) 方法研究身体成分与心脏代谢特征之间的因果关系。英国生物银行人群中与体脂量、无脂肪量和脂肪百分比相关的独立遗传变异被用作遗传工具变量,它们对循环系统疾病、2 型糖尿病、血糖特征和脂质分数的因果影响是从大型- 欧洲人群中的全基因组关联研究 (GWAS)。进行了单变量、多变量和双向 MR 分析。遗传预测的高脂肪量和脂肪百分比显着增加了大多数心脏代谢疾病的风险,并且在考虑脂肪量后,高无脂肪质量对大多数心脏代谢疾病具有保护作用。脂肪量、无脂肪量和脂肪百分比都与心房颤动和扑动、静脉曲张、深静脉血栓形成和肺栓塞的较高风险呈正相关。高脂肪量增加空腹血糖、稳态模型评估-胰岛素抵抗 (HOMA-IR)、甘油三酯、降低高密度脂蛋白胆固醇,高无脂肪量降低 HOMA-IR、甘油三酯和低密度脂蛋白胆固醇。遗传预测的无脂肪质量与 2 小时葡萄糖和总胆固醇呈双向负相关。

更新日期:2021-07-01
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