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Grant Details

Grant Number: 5R01CA052862-12 Interpret this number
Primary Investigator: Thomas, Duncan
Organization: University Of Southern California
Project Title: Survival Models for Genetic Epidemiology
Fiscal Year: 2004


Abstract

DESCRIPTION (provided by applicant): This project is primarily concerned with gene characterization for censored age-at-onset disease traits like cancer. During previous cycles, we have investigated a number of design issues for family-based studies, such as those arising in the context of our work on the NCI's Cooperative Family Registries for Breast and Colorectal Cancer Studies (CFRBCCS) as well as methods for modeling penetrance in relation to age and multiple genetic and environmental factors. The present proposal represents a continuation of work on these major themes. We propose to continue our efforts on methodologic issues in gene characterization, with the following aims: (i) Development of a unified likelihood framework for family-based association studies, including creation of a likelihood for segregation, linkage, direct association, and linkage disequilibrium for candidate genes, non-random ascertainment of families, censored age-at-onset phenotypes, estimation of penetrance from ascertained families with only some members genotyped, robust tests and variance estimators allowing for residual familial aggregation, multistage sampling of pedigrees, uncertainties in reported phenotype information in genetic analyses, implementation of these methods in the research version of the Genetic Analysis Package (GAP-A), and investigation of the relative efficiency of alternative study designs; (ii) Approaches to modeling complex disease traits, including methods for analysis of multiple phenotypes (e.g., multiple sites of cancer, such as the HNPCC syndrome), toxicokinetic models for complex metabolic pathways involving multiple genes and environmental exposures, and penetrance models incorporating genomic instability; (iii) Methods for characterizing the phenotypic effect of highly polymorphic genes; (iv) Methods for allowing for population stratification in case-control and cohort gene-association studies of unrelated individuals. To illustrate our methodologic work, we will draw examples from the CFRBCCS and other studies the genetic epidemiology of cancer in the USC Department of Preventive Medicine.



Publications

The Influence Of Screening For Precancerous Lesions On Family-based Genetic Association Tests: An Example Of Colorectal Polyps And Cancer
Authors: Schmit S.L. , Figueiredo J.C. , Cortessis V.K. , Thomas D.C. .
Source: American Journal Of Epidemiology, 2015-10-15 00:00:00.0; 182(8), p. 714-22.
PMID: 26306664
Related Citations

Influence Of Crtc1 Polymorphisms On Body Mass Index And Fat Mass In Psychiatric Patients And The General Adult Population
Authors: Choong E. , Quteineh L. , Cardinaux J.R. , Gholam-Rezaee M. , Vandenberghe F. , Dobrinas M. , Bondolfi G. , Etter M. , Holzer L. , Magistretti P. , et al. .
Source: Jama Psychiatry, 2013 Oct; 70(10), p. 1011-9.
PMID: 23925723
Related Citations

Gene-trait similarity regression for multimarker-based association analysis.
Authors: Tzeng J.Y. , Zhang D. , Chang S.M. , Thomas D.C. , Davidian M. .
Source: Biometrics, 2009 Sep; 65(3), p. 822-32.
PMID: 19210740
Related Citations

Design considerations in a sib-pair study of linkage for susceptibility loci in cancer.
Authors: Kerber R.A. , Amos C.I. , Yeap B.Y. , Finkelstein D.M. , Thomas D.C. .
Source: Bmc Medical Genetics, 2008-07-10 00:00:00.0; 9, p. 64.
EPub date: 2008-07-10 00:00:00.0.
PMID: 18616822
Related Citations

Hierarchical Bayes Prioritization Of Marker Associations From A Genome-wide Association Scan For Further Investigation
Authors: Lewinger J.P. , Conti D.V. , Baurley J.W. , Triche T.J. , Thomas D.C. .
Source: Genetic Epidemiology, 2007 Dec; 31(8), p. 871-82.
PMID: 17654612
Related Citations

Multistage Sampling For Latent Variable Models
Authors: Thomas D.C. .
Source: Lifetime Data Analysis, 2007 Dec; 13(4), p. 565-81.
PMID: 17943440
Related Citations

Viewpoint: Using Gene-environment Interactions To Dissect The Effects Of Complex Mixtures
Authors: Thomas,D.C. .
Source: Journal Of Exposure Science & Environmental Epidemiology, 2007 Dec; 17 Suppl 2, p. S71-4.
PMID: 18079767
Related Citations

Testing Association Between Disease And Multiple Snps In A Candidate Gene
Authors: Gauderman W.J. , Murcray C. , Gilliland F. , Conti D.V. .
Source: Genetic Epidemiology, 2007 Jul; 31(5), p. 383-95.
PMID: 17410554
Related Citations

Exploiting Gene-environment Interaction To Detect Genetic Associations
Authors: Kraft P. , Yen Y.C. , Stram D.O. , Morrison J. , Gauderman W.J. .
Source: Human Heredity, 2007; 63(2), p. 111-9.
PMID: 17283440
Related Citations

Testing Association And Linkage Using Affected-sib-parent Study Designs
Authors: Millstein J. , Siegmund K.D. , Conti D.V. , Gauderman W.J. .
Source: Genetic Epidemiology, 2005 Nov; 29(3), p. 225-33.
PMID: 16121357
Related Citations

Identifying Susceptibility Genes By Using Joint Tests Of Association And Linkage And Accounting For Epistasis
Authors: Millstein J. , Siegmund K.D. , Conti D.V. , Gauderman W.J. .
Source: Bmc Genetics, 2005; 6 Suppl 1, p. S147.
PMID: 16451607
Related Citations

Case-sibling Gene-association Studies For Diseases With Variable Age At Onset
Authors: Kraft P. , Thomas D.C. .
Source: Statistics In Medicine, 2004-12-15 00:00:00.0; 23(23), p. 3697-712.
PMID: 15534888
Related Citations

Toxicokinetic Genetics: An Approach To Gene-environment And Gene-gene Interactions In Complex Metabolic Pathways
Authors: Cortessis,V. , Thomas,D.C. .
Source: Iarc Scientific Publications, 2004; (157), p. 127-50.
PMID: 15055294
Related Citations

Class I And Ii Hla Genes Are Associated With Susceptibility And Age At Onset In Finnish Families With Type 1 Diabetes
Authors: Pitkäniemi,J. , Hakulinen,T. , Näsänen,J. , Tuomilehto-Wolf,E. , Tuomilehto,J. , DiMe Study Group .
Source: Human Heredity, 2004; 57(2), p. 69-79.
PMID: 15192279
Related Citations

Bayesian Modeling Of Complex Metabolic Pathways
Authors: Conti D.V. , Cortessis V. , Molitor J. , Thomas D.C. .
Source: Human Heredity, 2003; 56(1-3), p. 83-93.
PMID: 14614242
Related Citations

Proceedings Of The Genetic Analysis Workshop 13: Analysis Of Longitudinal Family Data For Complex Diseases And Related Risk Factors. November 11-14, 2002. New Orleans, Louisiana, Usa

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