We propose to develop our work on variance components methods for mapping QTLs for human complex traits using both association and linkage approaches. We will produce documentation for our existing programs for both stimulation and analysis and integrate these into a comprehensive package. We will extend our approach to include the interaction of QTLs with both the environment and with other loci, i.e., genotype X environment interaction and epistasis. We will include recent work on multivariate analysis with a view to increasing statistical power. We will generalize our analytic approach to a limited number of relatives other than sibs. One particularly novel aspect of our proposal is the development of a new test of association involving siblings which controls for population stratification and increases statistical power through the use of siblings selected for extreme scores on a continuous phenotype. This new test will be embedded in a maximum likelihood variance components approach where association will be modeled through sibling means and linkage will be modeled through the covariance matrix. This combined linkage-association test will yield novel information about the genetic architecture of complex traits. The transmission disequilibrium test will be rigorously developed for use with continuous traits either separately or combined with our new sibling test of association. The emphasis in our new proposal is on new approaches involving selected samples and maximum likelihood variance components analysis in order to achieve an integrated approach to mapping genes for complex traits.
| Garcia-Barcelo, Maria-Merce; Miao, Xiaoping; Tang, Clara S et al. (2011) No NRG1 V266L in Chinese patients with schizophrenia. Psychiatr Genet 21:47-9 |
| So, Hon-Cheong; Sham, Pak C (2011) Multiple testing and power calculations in genetic association studies. Cold Spring Harb Protoc 2011:pdb.top95 |
| Tang, C S; Sribudiani, Y; Miao, X P et al. (2010) Fine mapping of the 9q31 Hirschsprung's disease locus. Hum Genet 127:675-83 |
| Garcia-Barcelo, Maria-Merce; Yeung, Ming-Yiu; Miao, Xiao-Ping et al. (2010) Genome-wide association study identifies a susceptibility locus for biliary atresia on 10q24.2. Hum Mol Genet 19:2917-25 |
| Campbell, Desmond D; Sham, Pak C; Knight, Jo et al. (2010) Software for generating liability distributions for pedigrees conditional on their observed disease states and covariates. Genet Epidemiol 34:159-70 |
| Ehringer, Marissa A; McQueen, Matthew B; Hoft, Nicole R et al. (2010) Association of CHRN genes with ""dizziness"" to tobacco. Am J Med Genet B Neuropsychiatr Genet 153B:600-609 |
| Jawaid, A; Sham, P (2009) Impact and quantification of the sources of error in DNA pooling designs. Ann Hum Genet 73:118-24 |
| Brocklebank, D; Gayán, J; Andresen, J M et al. (2009) Repeat instability in the 27-39 CAG range of the HD gene in the Venezuelan kindreds: Counseling implications. Am J Med Genet B Neuropsychiatr Genet 150B:425-9 |
| Garcia-Barcelo, Maria-Merce; Tang, Clara Sze-Man; Ngan, Elly Sau-Wai et al. (2009) Genome-wide association study identifies NRG1 as a susceptibility locus for Hirschsprung's disease. Proc Natl Acad Sci U S A 106:2694-9 |
| Sham, P C; Cherny, S S; Purcell, S (2009) Application of genome-wide SNP data for uncovering pairwise relationships and quantitative trait loci. Genetica 136:237-43 |
Showing the most recent 10 out of 82 publications
