Power of sib-pair and sib-trio linkage analysis with assortative mating and multiple disease loci

Abstract

Sib-pair linkage analysis has been proposed for identifying genes that predispose to common diseases. We have shown that the presence of assortative mating and multiple disease-susceptibility loci (genetic heterogeneity) can increase the required sample size for affected-affected sib pairs several fold over the sample size required under random mating. We propose a new test statistic based on sib trios composed of either one unaffected and two affected siblings or one affected and two unaffected siblings. The sample-size requirements under assortative mating and multiple disease loci for these sib-trio statistics are much smaller, under most conditions, than the corresponding sample sizes for sib pairs. Study designs based on data from sib trios with one or two affected members are recommended whenever assortative mating and genetic heterogeneity are suspected.