Sham P C, Zhao J H, Curtis D
Department of Psychological Medicine, Institute of Psychiatry, London, England.
Ann Hum Genet. 1997 Jan;61(Pt 1):61-9. doi: 10.1046/j.1469-1809.1997.6110059.x.
Application of the affected sib-pair method of linkage analysis to sibships with variable numbers of affected and unaffected members requires a scheme for weighting the contributions from the sibships in the calculation of an overall test statistic. Currently accepted weighting schemes are based on the concepts of independent pairs and Shannon information content. Here, we show that the weighting scheme with maximum power to detect linkage can be determined from the theoretical means and variances of the sibship contributions under the null and alternative hypotheses. We derive the theoretical means and variances of the contributions from different types of sibships under a generalized single locus model. We use these theoretical means and variances to obtain the optimal weights for a variety of single locus models, and compare the power of existing weighting schemes relative to the optimum. The results suggest that, under a range of plausible assumptions, optimal power is nearly obtained by weighting to all sibpairs equally, except those occurring in sibships with so many affected siblings (usually five or more) that the probability of parental homozygosity for the disease allele becomes substantial. A corollary is that, in affected sib-pair analysis, the 'informativeness' of a sibship is more nearly proportional to the number of affected sib-pairs than to the number of affected siblings, up to about five affected siblings.
将连锁分析的受累同胞对法应用于受累和未受累成员数量可变的同胞组时，需要一种在计算总体检验统计量时对同胞组贡献进行加权的方案。目前公认的加权方案是基于独立对和香农信息含量的概念。在此，我们表明，具有最大连锁检测能力的加权方案可根据原假设和备择假设下同胞组贡献的理论均值和方差来确定。我们推导了广义单基因座模型下不同类型同胞组贡献的理论均值和方差。我们利用这些理论均值和方差获得各种单基因座模型的最优权重，并将现有加权方案的功效与最优方案进行比较。结果表明，在一系列合理假设下，除了那些受累同胞数量众多（通常为五个或更多）以至于疾病等位基因的亲本纯合概率变得显著的同胞组中的同胞对外，对所有同胞对同等加权几乎可获得最优功效。一个推论是，在受累同胞对分析中，同胞组的“信息量”与受累同胞对数量的近似比例关系比与受累同胞数量的关系更密切，直至约五个受累同胞。
