Khoury M J, James L M
Birth Defects and Genetic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333.
Am J Epidemiol. 1993 Jun 1;137(11):1241-50. doi: 10.1093/oxfordjournals.aje.a116626.
With increasing availability of polymorphic DNA markers, family studies can be used to identify linked susceptibility genes for chronic diseases. Nevertheless, in the presence of gene-environment interaction, the ability of family studies to detect associations between exposures and diseases has not been adequately compared with population studies. The authors derive and compare exposure relative risk measures obtained from population studies with those obtained from studying siblings of affected individuals. For multiplicative joint effects on disease risk between the gene and the exposure, it can be shown that exposure relative risks in siblings are identical to those obtained from the population. For less than multiplicative joint effects (e.g., additive) sibling relative risks are less than population relative risks. However, in the presence of more than multiplicative joint effects, it can be shown that sibling relative risks could be much higher than population relative risks, more so for dominant susceptibility genes than recessive ones, and depend on the model of gene-environment interaction. Under these conditions of strong gene-environment interaction, family studies can be useful in searching for exposure-disease associations, in addition to detecting underlying genetic mechanisms.
随着多态性DNA标记物的可获得性不断增加，家族研究可用于识别慢性疾病的连锁易感基因。然而，在存在基因-环境相互作用的情况下，家族研究检测暴露与疾病之间关联的能力尚未与人群研究进行充分比较。作者推导并比较了从人群研究中获得的暴露相对风险测量值与从研究受影响个体的兄弟姐妹中获得的测量值。对于基因与暴露之间对疾病风险的相乘联合效应，可以证明兄弟姐妹中的暴露相对风险与从人群中获得的风险相同。对于小于相乘的联合效应（例如相加效应），兄弟姐妹相对风险小于人群相对风险。然而，在存在大于相乘的联合效应的情况下，可以证明兄弟姐妹相对风险可能远高于人群相对风险，对于显性易感基因而言比隐性基因更是如此，并且取决于基因-环境相互作用的模型。在这些强基因-环境相互作用的条件下，除了检测潜在的遗传机制外，家族研究在寻找暴露-疾病关联方面可能会很有用。
