EFFECTIVENESS OF EXTREME DISCORDANT SIB PAIRS TO DETECT OLIGOGENIC DISEASE LOCI

A method for the genomic screening of quantitative traits using extrem e discordant sib pairs (EDSPs) has recently been described by Risch an d Zhang [1995; 1996]. For many models relevant to common, genetically complex diseases, EDSPs are the most powerful siblings for detecting l inkage. Thus, if such siblings can be identified and collected, powerf ul studies with reasonable genotyping budgets can be conducted. Using a subset of the GAW10 data, we have simulated a genomic screen using E DSPs. From the 4,780 total families in the first 20 replicates of 239 families, there were 100, 104, 155, 107, and 180 EDSP families for Q1, Q2, Q3, Q4, and Q5, respectively. EDSP data were analyzed for each tr ait using a modified version of MAPMAKER/SIBS capable of handling extr eme discordant sib pairs. Four regions, one for Q1, one for Q2, and tw o for Q4, were able to exceed a threshold for linkage corresponding to a 0.001 pointwise significance level. In three cases, maximum lod sco re (MLS) peaks occurred within 3.8 cM of a major gene. In the fourth c ase, the MLS peak occurred 28.4 cM from a major gene. Omission of pare nts and an alternative definition of EDSP were also investigated. (C) 1997 Wiley-Liss, Inc.