A clinically orientated approach for combining discordant and concordant sib pairs

The use of extreme discordant sib pairs (EDSP) or extreme concordant sib pairs (ECSP) has recently been proposed to increase power for mapping quantitative traits in humans (RISCH and ZHANG, 1995, 1996). In this paper we propose a test statistic to jointly analyze EDSP and ECSP based on a clinical sampling procedure. This test statistic does not fulfill any optimality criteria. However, this approach is useful for quantitative traits of clinical significance for which EDSP are rare and/or expensive to ascertain. We show how sample size calculations can be adjusted for recombination using single markers, multipoint analysis, incompletely polymorphic markers and varying proportions of ECSP. If the true genetic model is unknown, the combined approach appears to be more robust than sampling based on only EDSP or only ECSP. We discuss how to find the optimal proportion of EDSP and ECSP to be included in an analysis under power considerations.