Family Based Tests of Association for Complex Diseases

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DESCRIPTION (provided by applicant): The broad, long-term objective of this grant is to enable the discovery of genes underlying complex traits by the continued development of methods for family-based association tests. This class of tests has grown in popularity because they are robust to population admixture, and can be more powerful tests of linkage than conventional linkage tests in the presence of association between the trait and the marker. Interest in association strategies is growing with increasing recognition of the limitations of linkage strategies in localizing genes for complex diseases. Moreover, with the near completion of the map of the human genome, it will be feasible to obtain multiple single nucleotide polymorphisms (SNPs) in candidate genes of interest or regions of linkage; using multiple SNPs in family-based tests will provide a powerful strategy for finding disease genes. Initiatives devoted to the identification and mapping of SNP's throughout the genome are currently underway. Specifically, we plan to: 1. Develop several complementary tests for association between haplotypes composed from multiple tightly-linked markers and disease phenotypes when phase may be ambiguous and parents may not be available. 2. Develop new methods based on ranks for quantitative traits and time-to-onset data. 3. Develop an exact-test version of FBAT that will provide more accurate p-values when the number of informative families is small and/or a small alpha-level is used. 4. Incorporate analytic power calculations into FBAT which will enable users to determine the most powerful designs, select appropriate sample sizes and choose the most powerful tests. 5. Continue the development, updating, and maintenance of FBAT, our fully documented, user friendly software which provides a general strategy for implementing Family-Based Tests of Association (FBAT).