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 recoded the quantitative trait Q1 into a dichotomous trait using Q1 > or = 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 and control subjects were compared with respect to the number of alleles at one or more loci (0, 1, 2) that were identical-by-descent (IBD) with 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 marker D5G15 as associated with disease susceptibility (OR of sharing two alleles [share-2] = 7.7 [95% CI 2.5-23.9]). Our results were consistent with the results from Kruglyak and Lander's method of complete multipoint sib-pair analysis for linkage. For the marker (D5G15) identified through sib-pair analysis, we examined the effects of other covariates and evaluated gene-environment interaction using conditional logistic regression.