Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China.
J Clin Endocrinol Metab. 2023 Oct 18;108(11):e1245-e1252. doi: 10.1210/clinem/dgad308.
Observational studies have shown associations of birth weight (BW) with coronary heart disease (CHD), but results are inconsistent and do not distinguish the fetal or maternal effect of BW.
This study aims to explore the causal association between BW and CHD, analyze the fetal and maternal contribution, and quantify mediating effects of cardiometabolic factors.
Genetic variants from genome-wide association study summary-level data of own BW (N = 298 142), offspring BW (N = 210 267 mothers), and 16 cardiometabolic (anthropometric, glycemic, lipidemic, and blood pressure) factors were extracted as instrumental variables. We used two-sample Mendelian randomization study (MR) to estimate the causal effect of BW on CHD (60 801 cases and 123 504 controls from mixed ancestry) and explore the fetal and maternal contributions. Mediation analyses were conducted to analyze the potential mediating effects of 16 cardiometabolic factors using two-step MR.
Inverse variance weighted analysis showed that lower BW raised the CHD risk (β -.30; 95% CI: -0.40, -0.20) and consistent results were observed in fetal-specific/maternal-specific BW. We identified 5 mediators in the causal pathway from BW to CHD, including body mass index-adjusted hip circumference, triglycerides, fasting insulin, diastolic blood pressure, and systolic blood pressure (SBP), with mediated proportion ranging from 7.44% for triglycerides to 27.75% for SBP. Causality between fetal-specific and maternal-specific BW and CHD was mediated by glycemic factors and SBP, respectively.
Our findings supported that lower BW increased CHD risk and revealed that fetal-specific and maternal-specific BW may both contribute to this effect. The causality between BW and CHD was mediated by several cardiometabolic factors.
观察性研究表明出生体重（BW）与冠心病（CHD）之间存在关联，但结果不一致，且无法区分 BW 的胎儿或母体效应。
本研究旨在探讨 BW 与 CHD 之间的因果关系，分析胎儿和母体的贡献，并量化心脏代谢因素的中介作用。
从自身 BW（N=298142）、后代 BW（N=210267 位母亲）和 16 个心脏代谢（人体测量、血糖、血脂和血压）因素的全基因组关联研究汇总数据中提取遗传变异作为工具变量。我们使用两样本 Mendelian 随机化研究（MR）来估计 BW 对 CHD 的因果效应（来自混合血统的 60801 例病例和 123504 例对照），并探索胎儿和母体的贡献。使用两步 MR 分析了 16 个心脏代谢因素的潜在中介作用。
逆方差加权分析表明，较低的 BW 增加了 CHD 风险（β=-.30；95%CI：-0.40，-0.20），且在胎儿特异性/母体特异性 BW 中观察到一致的结果。我们在 BW 到 CHD 的因果途径中确定了 5 个中介物，包括体重指数调整的臀围、甘油三酯、空腹胰岛素、舒张压和收缩压（SBP），其中甘油三酯的中介比例为 7.44%，SBP 的中介比例为 27.75%。胎儿特异性和母体特异性 BW 与 CHD 之间的因果关系分别由血糖因素和 SBP 介导。
我们的研究结果支持 BW 降低会增加 CHD 风险的观点，并表明胎儿特异性和母体特异性 BW 可能都对这种效应有贡献。BW 与 CHD 之间的因果关系是由几个心脏代谢因素介导的。
