Skip Navigation
Grant Details

Grant Number: 5R01CA119225-04 Interpret this number
Primary Investigator: Zhao, Lue Ping
Organization: Fred Hutchinson Cancer Research Center
Project Title: Methods for Assessing Genetic Association with Time-Varying Phenotype
Fiscal Year: 2010
Back to top


Abstract

DESCRIPTION (provided by applicant): This is the revised proposal to the previously submitted RO1 CA119225-01. We appreciate the enthusiasm of the four reviewers and the entire review panel. Equally, we appreciate excellent suggestions to improve our research plan. In addition to clarifying numerous specific points, we have made several major revisions in accordance to reviewers' comments, which include: expansion of Aim 3 (for which the review panel has expressed a particular enthusiasm) at expense of leaving out Aim 4, proposal of a general hazard model to facilitate focused exploration of asymptotic properties for Aim 1 and 2, and reduction of five year proposal to four year proposal. As in the original proposal, our long-term objective is to develop innovative analytic methods for assessing genetic associations with clinical phenotypes, which are typically time-varying and/or censored. While our research does not directly involve humans, methods to be developed enable clinical investigators to design efficient studies, to integrate modern genetics into their research, to extract information efficiently, and to assist them in interpreting findings. Hence, the proposed research enhances our research capability of translating modern genetics into clinical research. Impacted research includes clinical trials, prospective cohort studies, or clinical follow-up studies. In particular, we are going to develop a set of new methods for correlating SNP-haplotypes with time-varying and censored phenotypes, with consideration to haplotypic association, diplotypic associations, gene-environmental interactions, competing risks and recurrences of phenotypes. Further, we will develop methods specifically for addressing phenotypic associations with patient's and donor's SNP-haplotypes, which arise from transplantation research. The preliminary exploration has shown the feasibility of our development. To ensure the practical relevance, we will motivate our development by the long term follow-up cohort of patients who have received bone marrow transplantation at our institution. All methods will be incorporated into the research program (HPIus), publicly available software. While developing methodologies is of priority in this project, we intend to implement all of the new methods into research program, and to release "working" programs to colleagues as soon as methods are accepted through peer review process. After extensive quality control, all working programs will be integrated into a software package, and will be made available to the community.

Back to top


Publications

Tumor evolution and intratumor heterogeneity of an oropharyngeal squamous cell carcinoma revealed by whole-genome sequencing.
Authors: Zhang XC, Xu C, Mitchell RM, Zhang B, Zhao D, Li Y, Huang X, Fan W, Wang H, Lerma LA, Upton MP, Hay A, Méndez E, Zhao LP
Source: Neoplasia, 2013 Dec;15(12), p. 1371-8.
PMID: 24403859
Related Citations

Back to top


Recursive organizer (ROR): an analytic framework for sequence-based association analysis.
Authors: Zhao LP, Huang X
Source: Hum Genet, 2013 Jul;132(7), p. 745-59.
EPub date: 2013 Mar 14.
PMID: 23494241
Related Citations

Back to top


Sequencing genes in silico using single nucleotide polymorphisms.
Authors: Zhang XC, Zhang B, Li SS, Huang X, Hansen JA, Zhao LP
Source: BMC Genet, 2012 Jan 30;13, p. 6.
EPub date: 2012 Jan 30.
PMID: 22289434
Related Citations

Back to top


Empirical evaluations of analytical issues arising from predicting HLA alleles using multiple SNPs.
Authors: Zhang XC, Li SS, Wang H, Hansen JA, Zhao LP
Source: BMC Genet, 2011 Apr 25;12, p. 39.
EPub date: 2011 Apr 25.
PMID: 21518453
Related Citations

Back to top


Predicting multiallelic genes using unphased and flanking single nucleotide polymorphisms.
Authors: Li SS, Wang H, Smith A, Zhang B, Zhang XC, Schoch G, Geraghty D, Hansen JA, Zhao LP
Source: Genet Epidemiol, 2011 Feb;35(2), p. 85-92.
EPub date: 2010 Dec 31.
PMID: 21254215
Related Citations

Back to top