Case-control studies of environmental influences in diseases with genetic determinants, with an application to Alzheimer's disease.
Case-control studies of environmental influences in diseases with genetic determinants, with an application to Alzheimer's disease.
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环境对具有遗传决定因素的疾病的影响的病例对照研究，并应用于阿尔茨海默病。
DOI：
10.1093/oxfordjournals.aje.a115869
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发表时间：
1991
影响因子：
5
通讯作者：
Woodbury,MA
中科院分区：
文献类型：
--
作者：
Breitner,JC;Murphy,EA;Woodbury,MA
许多疾病都有遗传和环境决定因素。有些需要两者，只有当一个脆弱的基因型在与环境因素相互作用后表达时，疾病表型才会出现。这些环境因素的检测在遗传原因引起的疾病中几乎没有得到优先考虑。特别是，这类疾病的病例对照研究可能会比较具有易感基因型的病例和大多缺乏易感基因型的对照之间的暴露。作者探讨了这类研究的可能结果，使用阿尔茨海默病作为一种疾病的例子，其中环境因素可能与必要的易感基因型相互作用，以加速疾病的表达。他们发现，对复杂遗传疾病中环境因素的病例对照研究通常会产生与易感个体之间的相对风险差异不大的比值比。然而，在极少数情况下，差异可能是严重的。这些研究的统计功效也与常见的已发表估计值一致，表明即使对照组大多不敏感，也几乎没有损失功效。然而，当病例对照方法应用于不一致的单卵双胞胎中时，在具有遗传决定因素的常见疾病的研究中，可能会增加功效。
Many diseases have both genetic and environmental determinants. Some require both, and the disease phenotype then appears only when a vulnerable genotype is expressed after interaction with environmental factors. The detection of such environmental factors has received little prior consideration in diseases with genetic causes. In particular, case-contsol studies of such diseases may compare exposures among cases, who have the susceptible genotype, and controls who mostly lack it. The authors explored the likely results of such studies, using the example of Alzheimer's disease as an illness where environmental factors may interact with a necessary susceptible genotype to accelerate disease expression. They found that case-control studies of environmental factors in complex genetic diseases will usually produce an odds ratio that differs little from the relative risk among susceptible individuals. In rare situations, however, the discrepancy may be gross. The statistical power of such studies also agrees well with familiar published estimates, suggesting that little power is lost even though the controls are mostly not susceptible. Power may be increased, however, in studies of common illnesses with genetic determinants when the case-control method is applied among discordant monozygotic twins.