Khoury M J, Beaty T H, Liang K Y
Department of Epidemiology, Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD 21205.
Am J Epidemiol. 1988 Mar;127(3):674-83. doi: 10.1093/oxfordjournals.aje.a114842.
Although familial aggregation has been shown for many if not all diseases, it is often difficult to determine whether such aggregation is due to shared genes or shared environmental factors. The authors examine the effect of familial aggregation of environmental risk factors on familial aggregation of disease when there is no genetic susceptibility. An environmental risk factor with a relative risk (R) for disease and population exposure frequency (f) is assumed to be clustered among siblings with varying degrees of sibling correlation in exposure (c). The impact of varying R, f, and c is examined on two common measures of familial aggregation: the relative risk of disease for siblings of cases compared with siblings of controls, and the sibling recurrence risk. It can be shown that both measures increase with increasing R and c, but decrease at high levels of f. However, even in the face of complete correlation in exposure among siblings (c = 1), environmental risk factors that have values of R less than 10 lead to modest sibling relative risks (ranging from 1 to 2) and low recurrence risks. Similar findings are obtained when familial aggregation of two additive environmental factors is considered. Because many diseases show higher sibling relative risks and recurrence risks, this analysis suggests that simple familial clustering of environmental factors is unlikely to account entirely for familial aggregation of disease, and that genetic factors ought to play an important role in causing familial aggregation.
尽管许多（即便不是所有）疾病都已显示出家族聚集性，但往往很难确定这种聚集是由于共享基因还是共享环境因素所致。作者研究了在不存在遗传易感性的情况下，环境危险因素的家族聚集性对疾病家族聚集性的影响。假设有一种对疾病具有相对风险（R）和人群暴露频率（f）的环境危险因素，在暴露方面具有不同程度同胞相关性（c）的同胞之间呈聚集状态。研究了R、f和c的变化对家族聚集性的两种常用衡量指标的影响：病例同胞与对照同胞相比的疾病相对风险，以及同胞复发风险。可以证明，这两种指标都随R和c的增加而增加，但在f值较高时会降低。然而，即使同胞之间在暴露方面完全相关（c = 1），R值小于10的环境危险因素导致的同胞相对风险也适中（范围为1至2）且复发风险较低。在考虑两种相加性环境因素的家族聚集性时也会得到类似的结果。由于许多疾病显示出更高的同胞相对风险和复发风险，该分析表明，环境因素的简单家族聚集不太可能完全解释疾病的家族聚集性，而且遗传因素在导致家族聚集方面应该起着重要作用。
