Whittemore A S, Tu I P
Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305-5405, USA.
Am J Hum Genet. 1998 May;62(5):1228-42. doi: 10.1086/301820.
Parametric-linkage analysis applied to large pedigrees with many affected individuals has helped in the identification of highly penetrant genes; but, for diseases lacking a clear Mendelian inheritance pattern or caused by several genes of low to moderate penetrance, a more robust strategy is nonparametric analysis applied to small sets of affected relatives, such as affected sib pairs. Here we show that the robustness of affected-sib-pair tests is related to the shape of the constraint set for the sibs' identity-by-descent (IBD) probabilities. We also derive a set of constraints for the IBD probabilities of affected sib triples and use common features of the shapes of the two constrain sets to introduce new nonparametric tests (called "minmax" tests) that are more robust than those in current use. Asymptotic-power computations support the robustness of the proposed minmax tests.
将参数连锁分析应用于有许多患病个体的大型家系，有助于识别高外显率基因；但是，对于缺乏明确孟德尔遗传模式或由几个低至中度外显率基因引起的疾病，一种更可靠的策略是将非参数分析应用于少量患病亲属，如患病同胞对。我们在此表明，患病同胞对检验的稳健性与同胞的同源性（IBD）概率的约束集形状有关。我们还推导了一组患病同胞三联体IBD概率的约束条件，并利用这两个约束集形状的共同特征引入了比现有检验更稳健的新非参数检验（称为“最小-最大”检验）。渐近功效计算支持了所提出的最小-最大检验的稳健性。
