A LINKAGE STRATEGY FOR DETECTION OF HUMAN QUANTITATIVE-TRAIT LOCI .2.OPTIMIZATION OF STUDY DESIGNS BASED ON EXTREME SIB PAIRS AND GENERALIZED RELATIVE RISK RATIOS

We are concerned here with practical issues in the application of extr eme sib-pair (ESP) methods to quantitative traits. Two important facto rs-namely, the way extreme trait values are defined and the proportion s in which different types of ESPs are pooled, in the analysis-are sho wn to determine the power and the cost effectiveness of a study design . We found that, in general, combining reasonable numbers of both extr emely discordant and extremely concordant sib pairs that were availabl e in the sample is more powerful and more cost effective than pursuing only a single type of ESP. We also found that dividing trait values w ith a less extreme threshold at one end or at both ends of the trait d istribution leads to more cost-effective designs. The notion of genera lized relative risk ratios (the lambda method, as described in the fir st part of this series of two articles) is used to calculate the power and sample size for various choices of polychotomization of trait val ues and for the combination of different types of ESPs. A balance then can be struck among these choices, to attain an optimum design.