Lawrence S, Beasley R, Doull I, Begishvili B, Lampe F, Holgate S T, Morton N E
Human Genetics Centre, University of Southampton, Princess Anne Hospital.
Ann Hum Genet. 1994 Oct;58(4):359-68. doi: 10.1111/j.1469-1809.1994.tb00732.x.
Traits related to atopy and asthma were defined in a random cohort of 131 families with three or more children. Correlation analysis provides no evidence of imprinting, maternal effect, or a major role of environment shared by sibs. Commingling analysis favours more than one distribution, the upper one being common for asthma and very common for atopy. Segregation analysis of rank-transformed variables provides only equivocal evidence of major genes against a polygenic background but suggests that such genes (if present) are individually common and not of large effect. Segregation analysis under a two-locus model gives consistent results with minimal distributional assumptions. To enter combined segregation analysis we favour a restricted model in which the major locus is additive on the liability scale and the pseudopolygenic modifier locus accounts for at least half the genetic variance. Total IgE and bronchial reactivity are proposed for meta-analysis of atopy and asthma respectively. Genetic analysis of complex inheritance is discussed and it is shown that allelic association with random loci is not a feasible approach.
在一个由131个有三个或更多孩子的家庭组成的随机队列中，对与特应性和哮喘相关的性状进行了定义。相关性分析没有提供印记、母体效应或同胞共享环境的主要作用的证据。混合分析支持不止一种分布，较高的一种分布在哮喘中常见，在特应性中非常常见。对秩转换变量的分离分析仅提供了在多基因背景下主要基因的模棱两可的证据，但表明此类基因（如果存在）个体常见且效应不大。在双基因座模型下的分离分析给出了一致的结果，且分布假设最少。为了进行联合分离分析，我们倾向于一个受限模型，其中主要基因座在易感性量表上是加性的，假多基因修饰基因座至少占遗传方差的一半。建议分别对总IgE和支气管反应性进行特应性和哮喘的荟萃分析。讨论了复杂遗传的遗传分析，并表明与随机基因座的等位基因关联不是一种可行的方法。
