Spectacular advances in knowledge about the human genome, and parallel advances in marker technology, have out paced the complementary development of methods in statistical genetics for complex traits. In response to this situation, the current proposal seeks support of our work on quantitative trait loci (QTL) mapping to accommodate data structures and models that are of practical importance to the design and analysis of modern genetic studies. Our revised renewal application is to support a collaborative effort from the Institute for Behavioral Genetics (University of Colorado), the Institute of Psychiatry (University of London), the Wellcome Trust Centre of Human Genetics (University of Oxford), and the Center for Statistical Genetics (University of Michigan). Our goal in the continuation of this productive collaboration is to further extend the methodology of variance components analysis to accommodate more general data structures and models that are of practical importance to the design and analysis of modern genetic studies, and to integrate these into a comprehensive software package. Specifically we will: 1) further develop methods for linkage and association analysis of selected samples that are not only robust and unbiased but also sufficiently efficient for application to general pedigrees; 2) develop models for epistasis and gene-environment (GE) interaction using optimal selection procedures for the detection of these interactive effects; 3) extend the Fulker et al (1999) model that partitions genotypic effects into between-sibships and within-sibship components from single locus allelic associations to multilocus haplotype associations; 4) develop variance-components methods that are able to accommodate genotyping errors; 5) refine a method for multipoint IBD calculations by use of regression (Fulker et al, 1995) to combine exact single-marker IBD information obtained from our software package, MERLIN; and 6) extend MERLIN into a comprehensive variance components analysis package for combined, multi-point linkage and association analysis of multivariate discrete and continuous data, for both selected and random samples.
| 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
