Multilocus linkage disequilibrium mapping of epistatic quantitative trait loci that regulate HIV dynamics: a simulation approach

The time-dependent change of HIV particle load, i.e. HIV dynamics, is likely to be controlled by a multitude of quantitative trait loci (QTL) that interact with each other as well as with various developmental and environmental factors in a coordinated manner. In this article, we have derived a new statistical model for mapping the epistatic QTL responsible for HIV dynamics in a natural human population. This model, constructed on the integrated theme of functional mapping and linkage disequilibrium (LD) mapping, can make use of information from multiple markers genotyped from the human genome. It allows for the test and estimation of genetic actions and interactions involved in the control of HIV progression and provides a general platform to identify the detailed genetic architecture of resistance or susceptibility of humans to HIV on a dynamic scale. We have generalized this model to accommodate various complicated clincal designs for AIDS studies. Simulation studies with different scenarios are performed to examine the statistical behaviour of the model. The genetic and statistical extensions of this mapping model to HIV/AIDS genomic research are discussed.