Program update and novel use of the DESPAIR program to design a genome-wide linkage study using relative pairs

Abstract

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.