Exploration of haplotype-based association methods for gene-mapping of complex traits

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Haplotype-based association methods for mapping genes have received increased interest recently because haplotypes capture the local linkage disequilibrium information in multiple linked markers and more informative than single markers. They have been shown to have good characteristics to map a gene in a homogenous population. The aim of the project is to clarify some basic questions regarding hablotype-based methods with respect to their power and validity in different situations regarding genetic heterogeneity, population stratification, genotyping errors, and missing data, using simulated data. Results will be incorporated into a new approach and recommendations made for the application of haplotype-based methods für genetic mapping of complex traits. We proposed novel extensions to improving the power of haplotype sharing analysis with a new approach based on the Mantel statistics. This work will be further developed with respect to the test statistics used, the measurement of genetic similarity, and the adjustment for multiple genetic or non-genetic factors. It will be implemented in public accessible software to ensure availability of the new developments for genetics studies.