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Grant Details

Grant Number: 5R01CA106320-08 Interpret this number
Primary Investigator: Zhao, Lue Ping
Organization: Fred Hutchinson Cancer Research Center
Project Title: Methods for Correlating Snp Haplotypes with Cancer
Fiscal Year: 2008
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Abstract

DESCRIPTION (provided by applicant): The long-term objectives of our research efforts are to develop innovative research design methods and analytic methods for the study of human diseases in the context of maturing genomic technologies (genetic polymorphisms, gene expressions and protein expressions). The primary aims of this proposal are to develop statistical methods and study designs to objectively assess the relationship of genetic polymorphisms in the form of SNPs and haplotypes with disease phenotypes and to investigate the role of gene-environment interactions, believed to play a major role in disease etiology. This objective represents the continuation of our current research project, which focuses on mapping complex diseases. Recent developments in genotyping technologies are revealing interesting local haplotype structures and are continuing to discover many more genetic markers throughout the genome. These provide not only unprecedented opportunities to gain a deeper understanding of disease etiology and to discover biomarkers useful for disease prevention and control, but also present a considerable challenge to the extraction of useful information from the ocean of genomic data now available. While extended pedigrees, nuclear families, sib-pairs have been used in indirect association analyses, direct association analyses may be more efficient and yield sufficient power to detect gene-environment interactions. Therefore, to maximize the power of the association analysis, case-control designs (both matched and unmatched) and cohort study designs will be applied. Methods to be developed will be based on well-established statistical techniques, including: genetic models, estimating equation techniques, likelihood methods, and logistic regression techniques. Where analytical solutions are not possible or computationally prohibitive, bootstrap techniques and Monte Carlo simulation methods will be applied to estimate relevant statistics. A range of statistical methods will be developed, including novel algorithms as necessary, and implemented for dissemination to the research community. Then these methods will be applied data from actual studies for validation and illustration purposes. To ensure the integration of statistics, biology and epidemiology, a team of investigators from multi-disciplinary backgrounds will discuss issues and jointly generate and critique statistical solutions.

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Publications

Deciphering Genome Environment Wide Interactions Using Exposed Subjects Only.
Authors: Zhao L.P. , Fan W. , Goodman G. , Radich J. , Martin P. .
Source: Genetic epidemiology, 2015 Jul; 39(5), p. 334-46.
EPub date: 2015-02-18.
PMID: 25694100
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Recursive organizer (ROR): an analytic framework for sequence-based association analysis.
Authors: Zhao L.P. , Huang X. .
Source: Human genetics, 2013 Jul; 132(7), p. 745-59.
EPub date: 2013-03-14.
PMID: 23494241
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Sequencing genes in silico using single nucleotide polymorphisms.
Authors: Zhang X.C. , Zhang B. , Li S.S. , Huang X. , Hansen J.A. , Zhao L.P. .
Source: BMC genetics, 2012-01-30; 13, p. 6.
EPub date: 2012-01-30.
PMID: 22289434
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Comparison of Two Methods for Detecting Alternative Splice Variants Using GeneChip() Exon Arrays.
Authors: Fan W. , Stirewalt D.L. , Radich J.P. , Zhao L. .
Source: International journal of biomedical science : IJBS, 2011 Sep; 7(3), p. 172-80.
PMID: 23675234
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Empirical evaluations of analytical issues arising from predicting HLA alleles using multiple SNPs.
Authors: Zhang X.C. , Li S.S. , Wang H. , Hansen J.A. , Zhao L.P. .
Source: BMC genetics, 2011-04-25; 12, p. 39.
EPub date: 2011-04-25.
PMID: 21518453
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Predicting multiallelic genes using unphased and flanking single nucleotide polymorphisms.
Authors: Li S.S. , Wang H. , Smith A. , Zhang B. , Zhang X.C. , Schoch G. , Geraghty D. , Hansen J.A. , Zhao L.P. .
Source: Genetic epidemiology, 2011 Feb; 35(2), p. 85-92.
EPub date: 2010-12-31.
PMID: 21254215
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A systematic search for SNPs/haplotypes associated with disease phenotypes using a haplotype-based stepwise procedure.
Authors: Yang Y. , Li S.S. , Chien J.W. , Andriesen J. , Zhao L.P. .
Source: BMC genetics, 2008-12-22; 9, p. 90.
EPub date: 2008-12-22.
PMID: 19102730
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Bias-reduced estimators and confidence intervals for odds ratios in genome-wide association studies.
Authors: Zhong H. , Prentice R.L. .
Source: Biostatistics (Oxford, England), 2008 Oct; 9(4), p. 621-34.
EPub date: 2008-02-28.
PMID: 18310059
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Observational studies, clinical trials, and the women's health initiative.
Authors: Prentice R.L. .
Source: Lifetime data analysis, 2007 Dec; 13(4), p. 449-62.
EPub date: 2007-10-18.
PMID: 17943443
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Epidemiologic methods developments: a look forward to the year 2032.
Authors: Prentice R.L. .
Source: Annals of epidemiology, 2007 Nov; 17(11), p. 906-10.
EPub date: 2007-09-14.
PMID: 17855116
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A haplotype-linkage analysis method for estimating recombination rates using dense SNP trio data.
Authors: Zhao L.P. , Li S.S. , Shen F. .
Source: Genetic epidemiology, 2007 Feb; 31(2), p. 154-72.
PMID: 17219374
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Empirical vs Bayesian approach for estimating haplotypes from genotypes of unrelated individuals.
Authors: Li S.S. , Cheng J.J. , Zhao L.P. .
Source: BMC genetics, 2007-01-29; 8, p. 2.
EPub date: 2007-01-29.
PMID: 17261196
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Aspects of the design and analysis of high-dimensional SNP studies for disease risk estimation.
Authors: Prentice R.L. , Qi L. .
Source: Biostatistics (Oxford, England), 2006 Jul; 7(3), p. 339-54.
EPub date: 2006-01-27.
PMID: 16443924
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HLA-E, HLA-F, and HLA-G polymorphism: genomic sequence defines haplotype structure and variation spanning the nonclassical class I genes.
Authors: Pyo C.W. , Williams L.M. , Moore Y. , Hyodo H. , Li S.S. , Zhao L.P. , Sageshima N. , Ishitani A. , Geraghty D.E. .
Source: Immunogenetics, 2006 May; 58(4), p. 241-51.
EPub date: 2006-03-29.
PMID: 16570139
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Toward understanding MHC disease associations: partial resequencing of 46 distinct HLA haplotypes.
Authors: Smith W.P. , Vu Q. , Li S.S. , Hansen J.A. , Zhao L.P. , Geraghty D.E. .
Source: Genomics, 2006 May; 87(5), p. 561-71.
EPub date: 2006-01-23.
PMID: 16434165
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A fine-scale linkage-disequilibrium measure based on length of haplotype sharing.
Authors: Wang Y. , Zhao L.P. , Dudoit S. .
Source: American journal of human genetics, 2006 Apr; 78(4), p. 615-28.
EPub date: 2006-02-13.
PMID: 16532392
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Genetic variation in bactericidal/permeability-increasing protein influences the risk of developing rapid airflow decline after hematopoietic cell transplantation.
Authors: Chien J.W. , Zhao L.P. , Hansen J.A. , Fan W.H. , Parimon T. , Clark J.G. .
Source: Blood, 2006-03-01; 107(5), p. 2200-7.
EPub date: 2005-11-22.
PMID: 16304058
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Toll-like receptor 4 polymorphisms are associated with resistance to Legionnaires' disease.
Authors: Hawn T.R. , Verbon A. , Janer M. , Zhao L.P. , Beutler B. , Aderem A. .
Source: Proceedings of the National Academy of Sciences of the United States of America, 2005-02-15; 102(7), p. 2487-9.
EPub date: 2005-02-07.
PMID: 15699327
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Evaluation of nine strategies for analyzing a cDNA toxicology microarray data set.
Authors: Zhang J.J. , Yi T. , Zhao L.P. .
Source: Journal of biopharmaceutical statistics, 2005; 15(3), p. 403-18.
PMID: 15920888
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