SIB-PAIR LINKAGE ANALYSES OF NUCLEAR FAMILY DATA - QUANTITATIVE VERSUS DICHOTOMOUS DISEASE CLASSIFICATION

Model-free sib-pair linkage analysis was used to screen 367 highly pol ymorphic markers for evidence of linkage to a disease, defined either quantitatively (Q1) or dichotomously (AF). Five individual replicates, plus a case family data set containing all families in these replicat es with at least one individual with AF, were analyzed. Sib-pair linka ge results for Q1 and AF varied considerably among the five replicates and did not consistently detect any of the three underlying major loc i, MG1, MG2, and MG3. For the pooled case families, linkage analyses o f Q1, but not AF, detected the flanking markers for MG1 and MG2 at the 0.05 and 0.01 levels, respectively. Overall, type 1 error rates were not elevated. The ability to analyze the disease quantitatively (Q1) a nd construct a data set more appropriate for linkage analysis (case fa milies) enhanced the power to detect at least some of the major loci u nderlying the disease. (C) 1997 Wiley-Liss, Inc.