DESIGN OF LINKAGE STUDIES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 DISHARE(配对设计)是一种计算机程序，可用于设计两阶段连锁研究，该研究使用相对配对进行二分表型。它决定了最优的两阶段研究设计--即，对于特定的功率和显著水平，应该研究多少对亲属，最初应该使用多少等距标记，以及应该使用什么标准来指定在第二阶段应该围绕其进行进一步搜索的标记。该程序将计算给定数量的第一阶段标记所需的相对配对数量或给定数量的相对配对所需的标记数量。我们强调使用最新版本的绝望来确定在候选感兴趣区域中额外的精细定位在多大程度上可以在先前的关联研究样本中导致力量的增加。我们还讨论了该程序的新特点，如对受影响和不协调的亲属对进行均值差检验，以及对完全同胞对等价物的估计，以设计当有多种类型亲属对可用时的研究。绝望是S.A.G.E.项目包的一部分，可以在网上免费使用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. DESPAIR (DESign for PAIRs) is a computer program useful for designing a two-stage linkage study using relative pairs for a dichotomous phenotype. It determines the optimal two-stage study design - i.e., for specified power and significance level, how many pairs of relatives should be studied, how many equally spaced markers should be used initially, and what criterion should be used to specify the markers around which further searching should be done at a second stage. The program will calculate either the number of relative pairs required for a given number of first-stage markers or the number of markers required for a given number of relative pairs. We highlight the use of the latest version of DESPAIR to decide to what extent additional fine mapping in a candidate region of interest can lead to an increase in power in a previous linkage study sample. We also discuss new features of the program, such as the mean difference test for affected and discordant relative pairs and estimation of full sibling pair equivalents to design a study when several types of relative pairs are available. DESPAIR is part of the S.A.G.E. program package and is freely available for use online.