Suzuki Etsuji, VanderWeele Tyler J
Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama, Japan,
Methods Mol Biol. 2015;1253:197-216. doi: 10.1007/978-1-4939-2155-3_11.
Under Bateson's original conception, the term "epistasis" is used to describe the situation in which the effect of a genetic factor at one locus is masked by a variant at another locus. Epistasis in the sense of masking has been termed "compositional epistasis." In general, statistical tests for interaction are of limited use in detecting compositional epistasis. Using recently developed epidemiological methods, however, it has been shown that there are relations between empirical data patterns and compositional epistasis. These relations can sometimes be exploited to empirically test for certain forms of compositional epistasis, by using alternative nonstandard tests for interaction.Using the counterfactual framework, we show conditions that can be empirically tested to determine whether there are individuals whose phenotype response patterns manifest epistasis in the sense of masking. Only under some very strong assumptions would tests for standard statistical interactions correspond to compositional epistasis. Even without such strong assumptions, however, one can still test whether there are individuals of phenotype response type representing compositional epistasis. The empirical conditions are quite strong, but the conclusions which tests of these conditions allow may be of interest in a wide range of studies. This chapter highlights that epidemiologic perspectives can be used to shed light on underlying mechanisms at the genetic, molecular, and cellular levels.
在贝特森最初的概念中，“上位性”一词用于描述一个基因座上的遗传因子的效应被另一个基因座上的变异所掩盖的情况。掩盖意义上的上位性被称为“组成型上位性”。一般来说，用于检测相互作用的统计检验在检测组成型上位性方面用途有限。然而，使用最近开发的流行病学方法已经表明，经验数据模式与组成型上位性之间存在关联。通过使用替代的非标准相互作用检验，有时可以利用这些关联对某些形式的组成型上位性进行实证检验。使用反事实框架，我们展示了可以进行实证检验的条件，以确定是否存在其表型反应模式表现出掩盖意义上的上位性的个体。只有在一些非常强的假设下，标准统计相互作用的检验才会对应于组成型上位性。然而，即使没有这样的强假设，仍然可以检验是否存在代表组成型上位性的表型反应类型的个体。实证条件相当严格，但这些条件检验所允许得出的结论在广泛的研究中可能会很有意义。本章强调，流行病学观点可用于阐明遗传、分子和细胞水平的潜在机制。
