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The goals of our analysis were to map functional loci, which contribute to the case-control status of a trait of interest, using large pedigrees. We used logistic regression fitted with the generalized estimation equation to test associations between a dichotomous phenotype and all genotyped common and rare single-nucleotide polymorphisms. In addition to the association study, we also developed and applied a simple and fast identical-by-descent-based test to identify loci that were shared among affected individuals more often than expected by chance. Among the top significant loci, we assessed the statistical power and the false discovery rate of both methods. We also demonstrated that family-based studies, compared with the standard population-based association studies, have great values and advantages for the discovery of multiple rare causal variants.

Identity by descent and association analysis of dichotomous traits based on large pedigrees