DESIGN OF LINKAGE STUDIES

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 DESPAIR（DESign for PAIRs）是一个计算机程序，可用于设计一个两阶段的连锁研究，使用相对对的二分法表型。它确定了最佳的两阶段研究设计-即，对于指定的功效和显著性水平，应研究多少对亲缘关系，最初应使用多少个等间距标记，以及应使用什么标准来指定在第二阶段应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对的数量或给定数量的相对对所需的标记的数量。我们强调使用最新版本的DESPAIR，以决定在何种程度上额外的精细映射在候选区域的利益可能会导致增加功率在以前的连锁研究样本。我们还讨论了该计划的新功能，如受影响的和不一致的相对对的平均差异检验和估计全同胞对等价物设计的研究时，几种类型的相对对可用。绝望是S.A.G.E.的一部分。程序包，并免费提供在线使用。

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.