THE METHOD OF SIB-PAIR LINKAGE ANALYSIS IN CONTEXT OF CASE-CONTROL DESIGN

We used sib-pair linkage analysis as part of an epidemiologic approach to solving Problem 2 of the GAW10 data set of nuclear families. We re coded the quantitative trait Q1 into a dichotomous trait using Q1 grea ter than or equal to 40 as the cut-point. In a case-control design of sib-pair analysis, the affected siblings of the proband were the case subjects and the unaffected siblings were the control subjects. Case a nd control subjects were compared with respect to the number of allele s at one or more loci (0,1,2) that were identical-by-descent (IBD) wit h those of the proband. Odds ratios (ORs) and 95% confidence intervals (95% CI) were then computed with subjects sharing no alleles (share-0 ) serving as the reference group. Significantly high ORs were taken as indication of linkage between a marker locus and a suspected disease- susceptibility locus. The case-control sib-pair analysis identified ma rker D5G15 as associated with disease susceptibility (OR of sharing tw o alleles [share-2] = 7.7 [95% CI 2.5-23.9]). Our results were consist ent with the results from Kruglyak and Lander's method of complete mul tipoint sib-pair analysis for linkage. For the marker (D5G15) identifi ed through sib-pair analysis, we examined the effects of other covaria tes and evaluated gene-environment interaction using conditional logis tic regression. (C) 1997 Wiley-Liss, Inc.