Khoury M J, Flanders W D, Lipton R B, Dorman J S
Birth Defects and Genetic Diseases Branch, Center for Environmental Health and Injury Control, Centers for Disease Control, Atlanta, Georgia 30333.
Genet Epidemiol. 1991;8(4):277-82. doi: 10.1002/gepi.1370080408.
The purpose of this commentary is to provide a framework for using the well-known sib-pair methodology in the context of epidemiologic study designs. Using examples from the Pittsburgh family studies of insulin-dependent diabetes mellitus, we illustrate that the sib-pair method can be used in family-based epidemiologic studies. In a cohort study, unaffected relatives of probands ascertained from well-defined populations are followed for disease development. Disease risks are then stratified according to the number of alleles at one or more loci (0, 1, 2) that are identical by descent (ibd) with the proband. In the absence of linkage between the marker locus and the disease locus, disease risks are expected to be identical in the three groups. Measures of relative risk can be computed (with share-0 as baseline group). In a case-control study, relatives of probands that become affected (cases) are compared to a sample of relatives of probands that stay unaffected (controls) with respect to the number of alleles ibd with the proband. Measures of odds ratio can be computed (with share-0 as baseline group). In both cohort and case-control approaches, covariates including other genetic markers and environmental exposures can be evaluated in relation to disease risk and also for evidence of interaction with the specific marker of interest using stratified and multivariate analyses. Family-based epidemiologic studies allow investigators to study, in a single design, the role of environmental factors and specific gene loci in the etiology of diseases.
本评论的目的是提供一个框架，以便在流行病学研究设计的背景下使用著名的同胞对方法。通过匹兹堡胰岛素依赖型糖尿病家庭研究中的例子，我们说明同胞对方法可用于基于家庭的流行病学研究。在队列研究中，对从明确界定的人群中确定的先证者的未患病亲属进行疾病发展跟踪。然后根据与先证者同源相同（ibd）的一个或多个基因座上等位基因的数量（0、1、2）对疾病风险进行分层。在标记基因座与疾病基因座之间不存在连锁的情况下，预计三组中的疾病风险相同。可以计算相对风险度量（以共享0组作为基线组）。在病例对照研究中，将患病的先证者亲属（病例）与未患病的先证者亲属样本（对照）在与先证者同源相同的等位基因数量方面进行比较。可以计算比值比度量（以共享0组作为基线组）。在队列研究和病例对照研究方法中，包括其他遗传标记和环境暴露在内的协变量可以根据疾病风险进行评估，也可以使用分层分析和多变量分析来评估与感兴趣的特定标记相互作用的证据。基于家庭的流行病学研究使研究人员能够在单一设计中研究环境因素和特定基因座在疾病病因中的作用。
