? 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). ? ?
| Hoffmann, Thomas J; Vansteelandt, Stijn; Lange, Christoph et al. (2011) Combining disease models to test for gene-environment interaction in nuclear families. Biometrics 67:1260-70 |
| VanderWeele, Tyler J; Laird, Nan M (2011) Tests for compositional epistasis under single interaction-parameter models. Ann Hum Genet 75:146-56 |
| Hoffmann, Thomas J; Lange, Christoph; Vansteelandt, Stijn et al. (2010) Parsing the effects of individual SNPs in candidate genes with family data. Hum Hered 69:91-103 |
| Ding, Xiao; Laird, Nan (2009) Family-Based Association Tests with longitudinal measurements: handling missing data. Hum Hered 68:98-105 |
| Hoffmann, Thomas J; Laird, Nan M (2009) fgui: A Method for Automatically Creating Graphical User Interfaces for Command-Line R Packages. J Stat Softw 30: |
| Ionita-Laza, Iuliana; Lange, Christoph; M Laird, Nan (2009) Estimating the number of unseen variants in the human genome. Proc Natl Acad Sci U S A 106:5008-13 |
| Hoffmann, Thomas J; Lange, Christoph; Vansteelandt, Stijn et al. (2009) Gene-environment interaction tests for dichotomous traits in trios and sibships. Genet Epidemiol 33:691-9 |
| Vansteelandt, Stijn; Demeo, Dawn L; Lasky-Su, Jessica et al. (2008) Testing and estimating gene-environment interactions in family-based association studies. Biometrics 64:458-67 |
| Degnan, James H; Lasky-Su, Jessica; Raby, Benjamin A et al. (2008) Genomics and genome-wide association studies: an integrative approach to expression QTL mapping. Genomics 92:129-33 |
| Ionita-Laza, Iuliana; Laird, Nan M; Raby, Benjamin A et al. (2008) On the frequency of copy number variants. Bioinformatics 24:2350-5 |
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