Multilocus Linkage Analysis of Affected Sib Pairs

Abstract

Objective: The conventional affected sib pair methods evaluate the linkage information at a locus by considering only marginal information. We describe a multilocus linkage method that uses both the marginal information and information derived from the possible interactions among several disease loci, thereby increasing the significance of loci with modest effects. Methods: Our method is based on a statistic that quantifies the linkage information contained in a set of markers. By a marker selection-reduction process, we screen a set of polymorphisms and select a few that seem linked to disease. Results: We test our approach on genome scan data for inflammatory bowel disease (InfBD) and on simulated data. On real data we detect 6 of the 8 known InfBD loci; on simulated data we obtain improvements in power of up to 40% compared to a conventional single-locus method. Conclusion: Our extensive simulations and the results on real data show that our method is in general more powerful than single-locus methods in detecting disease loci responsible for complex traits. A further advantage of our approach is that it can be extended to make use of both the linkage and the linkage disequilibrium between disease loci and nearby markers.