Effect of Two- and Three-Locus Linkage Disequilibrium on the Power to Detect Marker/Phenotype Associations

There has been much recent interest in describing the patterns of linkage disequilibrium (LD) along a chromosome. Most empirical studies that have examined this issue have concentrated on LD between collections of pairs of markers and have not considered the joint effect of a group of markers beyond these pairwise connections. Here, we examine many different patterns of LD defined by both pairwise and joint multilocus LD terms. The LD patterns we considered were chosen in part by examining those seen in real data. We examine how changes in these patterns affect the power to detect association when performing single-marker and haplotype-based case-control tests, including a novel haplotype test based on contrasting LD between affected and unaffected individuals. Through our studies we find that differences in power between single-marker tests and haplotype-based tests in general do not appear to be large. Where moderate to high levels of multilocus LD exist, haplotype tests tend to be more powerful. Single-marker tests tend to prevail when pairwise LD is high. For moderate pairwise values and weak multilocus LD, either testing strategy may come out ahead, although it is also quite likely that neither has much power.