An evaluation of affected-sib-pair methods and transmission/disequilibriumtests for detecting genes underlying a complex trait

For the analysis of complex traits, it is of interest to compare a few nonp arametric methods such as affected-sib-pair (ASP) analyses and transmission /disequilibrium tests (TDT). The affected-sib-pair approaches we have exami ned here are ASP and ALL-SP which are implemented in SIBPAIR program. We al so applied the BETA program which has not so far been extensively compared with other methods. The study indicates that the ASP program and the BETA p rogram give concordant results although BETA tends to give higher lod score s. However, when all sibs were included in the analysis (ALL-SP), linkage s ignals became weaker, compared with ASP and BETA. The TDT detected 66 posit ive signals at a significance level of 0.05 and identified a true locus. Ov erall, our results suggest that affected-sib-pair analysis has reasonable p ower (p < 0.0001) to detect linkage given the disease model and the family structure specified in the GAW11 Problem 2 data set. (C) 1999 Wiley-Liss, I nc.