Medical Research Council Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, United Kingdom.
Population Health Sciences, Bristol Medical School, University of Bristol, Barley House, Oakfield Grove, Bristol, United Kingdom.
Elife. 2022 Mar 18;11:e72984. doi: 10.7554/eLife.72984.
Taller people have a lower risk of coronary heart disease but a higher risk of many cancers. Mendelian randomization (MR) studies in unrelated individuals (population MR) have suggested that these relationships are potentially causal. However, population MR studies are sensitive to demography (population stratification, assortative mating) and familial (indirect genetic) effects.
In this study, we performed within-sibship MR analyses using 78,988 siblings, a design robust against demography and indirect genetic effects of parents. For comparison, we also applied population MR and estimated associations with measured height.
Within-sibship MR estimated that 1 SD taller height lowers the odds of coronary heart disease by 14% (95% CI: 3-23%) but increases the odds of cancer by 18% (95% CI: 3-34%), highly consistent with population MR and height-disease association estimates. There was some evidence that taller height reduces systolic blood pressure and low-density lipoprotein cholesterol, which may mediate some of the protective effects of taller height on coronary heart disease risk.
For the first time, we have demonstrated that the purported effects of height on adulthood disease risk are unlikely to be explained by demographic or familial factors, and so likely reflect an individual-level causal effect. Disentangling the mechanisms via which height affects disease risk may improve the understanding of the etiologies of atherosclerosis and carcinogenesis.
This project was conducted by researchers at the MRC Integrative Epidemiology Unit (MC_UU_00011/1) and also supported by a Norwegian Research Council Grant number 295989.
高个子人群患冠心病的风险较低，但患多种癌症的风险较高。在无关联个体中进行的孟德尔随机化（Mendelian randomization，MR）研究（人群 MR）表明，这些关系可能具有因果关系。然而，人群 MR 研究易受人口统计学因素（人群分层、选择性交配）和家族因素（间接遗传）的影响。
在这项研究中，我们使用 78988 对兄弟姐妹进行了同胞内 MR 分析，该设计可有效抵抗人口统计学和父母间接遗传效应的影响。为了进行比较，我们还应用了人群 MR，并估计了与身高测量值的关联。
同胞内 MR 估计，身高每增加 1 个标准差，冠心病的发病风险降低 14%（95%置信区间：3-23%），而癌症的发病风险增加 18%（95%置信区间：3-34%），这与人群 MR 和身高与疾病关联的估计结果高度一致。有一些证据表明，身高较高可降低收缩压和低密度脂蛋白胆固醇，这可能部分解释了身高对冠心病风险的保护作用。
我们首次证明，身高对成年期疾病风险的影响不太可能由人口统计学或家族因素来解释，因此很可能反映了个体层面的因果效应。通过分离身高影响疾病风险的机制，可能有助于深入了解动脉粥样硬化和癌变的发病机制。
本项目由 MRC 综合流行病学单位（MC_UU_00011/1）的研究人员开展，并得到挪威研究理事会 295989 号资助。
