Mendelian randomisation analyses find pulmonary factors mediate the effect of height on coronary artery disease
Mendelian randomisation analyses find pulmonary factors mediate the effect of height on coronary artery disease
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DOI：
10.1038/s42003-019-0361-2
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发表时间：
2019-03-27
影响因子：
5.9
通讯作者：
Deloukas, Panos
中科院分区：
文献类型：
--
作者：
Marouli, Eirini;Del Greco, M. Fabiola;Deloukas, Panos
有证据表明，较低的身高与冠状动脉疾病（CAD）的高风险和2型糖尿病（T2D）的高风险相关。但目前尚不清楚这些关联是因果关系、直接关系还是由其他因素介导。在这里，我们表明，基因决定的身高（类似于6.5厘米）高一个标准差与冠心病风险降低16%有因果关系（OR = 0.84, 95% CI 0.80-0.87）。在进行放松多效性假设的敏感性分析后，这种因果关系仍然存在。在调整了潜在的介质（血脂、血压、血糖特征、体重指数、社会经济地位）后，身高对冠心病风险的因果影响降低了1-3%。相反，我们的数据表明，肺功能（通过用力呼气量[FEV1]和用力肺活量[FVC]测量）是身高对CAD影响的中介。我们没有观察到身高对T2D风险的直接因果关系。
There is evidence that lower height is associated with a higher risk of coronary artery disease (CAD) and increased risk of type 2 diabetes (T2D). It is not clear though whether these associations are causal, direct or mediated by other factors. Here we show that one standard deviation higher genetically determined height (similar to 6.5 cm) is causally associated with a 16% decrease in CAD risk (OR = 0.84, 95% CI 0.80-0.87). This causal association remains after performing sensitivity analyses relaxing pleiotropy assumptions. The causal effect of height on CAD risk is reduced by 1-3% after adjustment for potential mediators (lipids, blood pressure, glycaemic traits, body mass index, socio-economic status). In contrast, our data suggest that lung function (measured by forced expiratory volume [FEV1] and forced vital capacity [FVC]) is a mediator of the effect of height on CAD. We observe no direct causal effect of height on the risk of T2D.