Robust Methods for Complex Trait Association Mapping

Univ Of North Carolina Chapel Hill, Chapel Hill NC

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Abstract

The objectives of this research are to address some statistical issues related to association mapping (or disequilibrium mapping) for complex traits. We plan to develop robust, yet efficient statistical methods to deal with some important problems that have not been addressed or have not been fully resolved in the literature. The specific aims are: 1. To develop simple and robust techniques for assessing population stratification when anonymous markers are available, but are not necessarily in linkage equilibrium with each other. 2. To develop an efficient method for capturing the simultaneous effects of multiple genetic variants that individually make only a small contribution to the total disease risk, while controlling the overall false positive rate. 3. To explore robust non-parametric methods for estimating and assessing haplotypes associated with disease: mapping disease-associated haplotypes without pre-assigning window size of the haplotype; mapping multiple pre-disposing haplotypes; and mapping when haplotypes cannot be discerned unambiguously. Software to carry out the specific aims will be developed and implemented in the R or C computing environment for public distribution.