PDF(Pubmed)
Abstract：
An inverse correlation between stature and risk of coronary artery disease (CAD) has been observed in several epidemiologic studies, and recent Mendelian randomization (MR) experiments have suggested causal association. However, the extent to which the effect estimated by MR can be explained by cardiovascular, anthropometric, lung function, and lifestyle-related risk factors is unclear, with a recent report suggesting that lung function traits could fully explain the height-CAD effect. To clarify this relationship, we utilized a well-powered set of genetic instruments for human stature, comprising >1,800 genetic variants for height and CAD. In univariable analysis, we confirmed that a one standard deviation decrease in height (~6.5 cm) was associated with a 12.0% increase in the risk of CAD, consistent with previous reports. In multivariable analysis accounting for effects from up to 12 established risk factors, we observed a >3-fold attenuation in the causal effect of height on CAD susceptibility (3.7%, p = 0.02). However, multivariable analyses demonstrated independent effects of height on other cardiovascular traits beyond CAD, consistent with epidemiologic associations and univariable MR experiments. In contrast with published reports, we observed minimal effects of lung function traits on CAD risk in our analyses, indicating that these traits are unlikely to explain the residual association between height and CAD risk. In sum, these results suggest the impact of height on CAD risk beyond previously established cardiovascular risk factors is minimal and not explained by lung function measures.
摘要：
在一些流行病学研究中观察到身高与冠状动脉疾病（CAD）风险之间的负相关，最近的孟德尔随机化（MR）实验表明了因果关系。然而,磁共振估计的影响在多大程度上可以用心血管解释，人体测量学,肺功能,与生活方式相关的危险因素尚不清楚，最近的一份报告表明，肺功能特征可以完全解释身高CAD效应。为了澄清这种关系，我们利用了一套强大的基因仪器来检测人类的身材，包括>1800个身高和CAD的遗传变异。在单变量分析中，我们证实，身高下降1个标准差（~6.5cm）与CAD风险增加12.0%相关，与以前的报告一致。在多变量分析中，考虑了多达12个既定风险因素的影响，我们观察到身高对CAD易感性的因果效应衰减>3倍(3.7%，p=0.02)。然而,多变量分析表明，身高对CAD以外的其他心血管性状的独立影响，与流行病学关联和单变量MR实验一致。与已发表的报告相比，在我们的分析中，我们观察到肺功能特征对CAD风险的影响最小，表明这些特征不太可能解释身高和CAD风险之间的残余关联。总之,这些结果提示,身高对CAD风险的影响在先前确定的心血管危险因素之外很小,不能通过肺功能测量来解释.
