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Adv Genet. 2008;60:407-35. doi: 10.1016/S0065-2660(07)00415-4.

Characterization of LD structures and the utility of HapMap in genetic association studies.

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Division of Biostatistics and Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.


Observed distribution of and variation in linkage disequilibrium (LD) with respect to the evolution history and disease transmission in a population is the driving force behind the current wave of genome-wide association (GWA) studies of complex human diseases. An extensive literature covers topics from haplotype analysis that utilizes local LD structures in candidate genes and regions to genome-wide organization of LD blocks (neighborhood) that led to the development of International HapMap Project and panels of "tagSNPs" used by current GWA studies. In this chapter, we examine the scenarios where each of the major types of analysis methods may be applicable and where the current popular genotyping platforms for GWA might come short. We discuss current association analysis methods by emphasizing their reliance on the local LD structures or the global organization of the LD structures, and highlight the need to consider individual marker information content in large-scale association mapping.

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