Mortality differences by APOE genotype estimated from demographic synthesis
Mortality differences by APOE genotype estimated from demographic synthesis
复制标题
DOI：
10.1002/gepi.0164
复制
发表时间：
2002-02-01
影响因子：
2.1
通讯作者：
Ewbank, DC
中科院分区：
文献类型：
--
作者：
Ewbank, DC
载脂蛋白 E (APOE) 4 等位基因与低死亡率人群中两种主要死亡原因的风险增加相关：缺血性心脏病和阿尔茨海默病。与年轻人相比，这种情况在百岁老人中较少见。因此，它很可能与死亡风险过高有关。本文扩展了人口模型，该模型估计基因频率随年龄变化的相对死亡风险。由此产生的人口统计综合将基因频率与队列研究中按基因型划分的死亡率数据结合起来。该模型适用于丹麦、芬兰、法国、意大利、瑞典和美国的数据。接近 50 岁时，3/4 基因型的死亡风险是 3/3 基因型的 1.34 倍 (95% Cl 1. 18-1.67)。 4/4 的相对风险是 3/4 的相对风险的平方，即 1.81。 2/3 基因型具有保护性，在 50 岁左右的相对风险为 0.84 (0.68-0.93)。这些相对风险在最大年龄时趋向于 1.0，而 APOE 基因型与 100 岁以上死亡率变化不大相关。不同性别的相对风险没有显着差异。几乎没有证据表明欧洲内部 APOE 的效果存在差异。这种方法可以推广到结合来自各种研究设计和样本特征的疾病遗传风险因素的数据。热内特.流行病。 22:146-155, 2002。(C) 2002 Wiley-Liss。公司
The 4 allele of apolipoprotein E (APOE) is associated with increased risk of two major causes of death in low-mortality populations: ischemic heart disease and Alzheimer's disease. It is less common among centenarians than at younger ages. Therefore, it is likely that it is associated with excess risk of death. This article extends demographic models that estimate relative mortality risks from changes in gene frequencies with age. The resulting demographic synthesis combines gene frequencies with data on mortality by genotype from cohort studies. The model was applied to data from Denmark, Finland, France, Italy, Sweden, and the United States. Near age 50, the 3/4 genotype is associated with a risk of death of 1.34 times that of the 3/3 (95% Cl 1. 18-1.67). The relative risk for 4/4 is the square of the relative risk for 3/4, 1.81. The 2/3 genotype is protective with a relative risk of 0.84 (0.68-0.93) near age 50. These relative risks move toward 1.0 at the oldest ages and APOE genotype is associated with little variation in mortality over age 100. There are no significant differences in the relative risks by sex. There is little evidence of differences within Europe in the effects of APOE. This approach can be generalized to combine data on genetic risk factors for disease from a wide variety of study designs and sample characteristics. Genet. Epidemiol. 22:146-155, 2002. (C) 2002 Wiley-Liss. Inc.