2-LOCUS DISEASE-MODELS WITH 2-MARKER LOCI - THE POWER OF AFFECTED-SIB-PAIR TESTS

Recently, Schork et al. found that two-trait-locus, two-marker-locus ( parametric) linkage analysis can provide substantially mole linkage in formation than can standard one-trait-locus, one-marker-locus methods. However, because of the increased burden of computation, Schork et al . do not expect that their approach will be applied in an initial geno me scan. Further, the specification of a suitable two-locus segregatio n model can be crucial. Affected-sib-pair tests are computationally si mple and do not require an explicit specification of the disease model . In the past, however, these tests mainly have been applied to data w ith a single marker Locus. Here, we consider sib-pair tests that make it possible to analyze simultaneously two marker loci. The power of th ese tests is investigated for different (epistatic and heterogeneous) two-trait-locus models, each trait locus being linked to one of the ma rker loci. We compare these tests both with the test that is optimal f or a certain model and with the strategy that analyzes each marker loc us separately. The results indicate that a straightforward extension o f the well-known mean test for two marker loci can be much more powerf ul than single-marker-locus analysis and that its power is only slight ly inferior to the power of the optimal test.