Center for Non-communicable Disease Management, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Department of Epidemiology, Capital Institute of Pediatrics, Beijing, China.
Nutr Metab Cardiovasc Dis. 2022 Jul;32(7):1753-1765. doi: 10.1016/j.numecd.2022.03.030. Epub 2022 Apr 10.
Observational studies reveal that different body fat measures are associated with cardiometabolic disease with different effects. However, causality is not reflected by such observations. To explore and compare the causal relationships of general obesity (measured by body mass index (BMI)), adipose obesity (measured by fat mass percentage (FMP)) and central obesity (measured by waist-to-height ratio (WHtR)) with cardiometabolic traits among children.
We conducted one sample Mendelian randomization (MR) analysis in 3266 children from Beijing Children and Adolescents Metabolic Syndrome Study. Genetic instruments based on 28 SNPs were performed to explore and compare the causal associations of genetically BMI, FMP and WHtR with cardiometabolic traits. The genetic instruments were robustly correlated with observed BMI, FMP and WHtR. Each genetically 1-SD increment in BMI, FMP and WHtR were causally associated with increment in systolic blood pressure (SBP), diastolic blood pressure (DBP), log-transformed fasting plasma glucose (FPG), log-transformed HOMA-β, and decrease in log-transformed high-density lipoprotein cholesterol (HDL), respectively (all P < 0.05 after Bonferroni correction). The receiver operating characteristic curve indicated that BMI and FMP showed stronger effects on SBP, DBP, HOMA-β and HDL than WHtR (all P < 0.05). We also observed causal associations of BMI and FMP with log-transformed fasting insulin and HOMA-IR.
The MR analysis based on population-based cohort indicated a causal relationship of adiposity and body fat distribution with cardiometabolic traits. When compared with central obesity, general obesity and adipose obesity might own stronger effects on blood pressure and blood lipids among children.
观察性研究表明，不同的体脂测量方法与代谢心血管疾病的相关性不同，影响也不同。然而，这种观察并不能反映因果关系。本研究旨在探讨和比较儿童总体肥胖（用体质指数（BMI）衡量）、脂肪肥胖（用脂肪百分比（FMP）衡量）和中心性肥胖（用腰高比（WHtR）衡量）与代谢心血管特征之间的因果关系。
我们在北京儿童青少年代谢综合征研究中对 3266 名儿童进行了单样本孟德尔随机化（MR）分析。采用基于 28 个 SNP 的遗传工具，探讨和比较了遗传 BMI、FMP 和 WHtR 与代谢心血管特征的因果关系。遗传工具与观察到的 BMI、FMP 和 WHtR 具有稳健的相关性。BMI、FMP 和 WHtR 每增加 1-SD，收缩压（SBP）、舒张压（DBP）、空腹血浆葡萄糖（FPG）的自然对数值、HOMA-β的自然对数值和高密度脂蛋白胆固醇（HDL）的自然对数值分别增加（经 Bonferroni 校正后所有 P 值均<0.05）。受试者工作特征曲线表明，BMI 和 FMP 对 SBP、DBP、HOMA-β 和 HDL 的影响大于 WHtR（所有 P 值均<0.05）。我们还观察到 BMI 和 FMP 与空腹胰岛素和 HOMA-IR 的自然对数值之间存在因果关系。
基于人群的队列的 MR 分析表明，肥胖和体脂分布与代谢心血管特征存在因果关系。与中心性肥胖相比，总体肥胖和脂肪肥胖可能对儿童的血压和血脂有更强的影响。
