Qtl Mapping With Discordant And Concordant Sibling Pairs: New Statistics And New Design Strategies

The term "extreme discordant and concordant" (EDAC) sampling has been used to describe a variety of strategies for quantitative trait locus mapping using sibling pairs sampled from the corners of the bivariate trait distribution. The principle of the design is to gain efficiency by genotyping only the most informative of the available sibling pairs. EDAC-type designs have been studied in a number of papers, and have been applied in a few others. This literature is somewhat out of date, however, because there are many new statistics that are appropriate for EDAC data. With newer statistics, the power of EDAC designs can be improved. Moreover, the relative power of different designs must be re-evaluated, because the newer statistics improve the power of some designs more than others. That is, there is a circular relationship between design and statistic choices. In this report, we review a number of available design and statistic choices for EDAC studies, and use simulation to show what statistics are most powerful for each design. We then use those more powerful statistics to suggest strategies for making design choices among various EDAC and non-EDAC designs that use sibling pairs. We find that when genotyping must be minimized, an EDAC design with predominantly discordant pairs is the best choice, and when a balance of genotyping and phenotyping effort must be achieved, single proband ascertainment can do better. We also show that moderately selected samples (as opposed to very extreme samples) can be an efficient choice for many studies. (c) 2005 Wiley-Liss, Inc.