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Grant Details

Grant Number: 5R03CA171011-03 Interpret this number
Primary Investigator: Biswas, Swati
Organization: University Of Texas Dallas
Project Title: Identifying Rare Haplotype-Environment Interactions Using Logistic Bayesian Lasso
Fiscal Year: 2013


Abstract

DESCRIPTION (provided by applicant): Rare variants have been heralded as key to uncovering \missing heritability" in complex diseases such as cancers. These variants can now be genotyped using next-generation sequencing technologies; nonetheless, rare haplotypes may also result from combination of common SNPs available from Genome-Wide Association Studies (GWAS). In this regard, there may be a great deal of treasure that are yet to be mined from the GWAS data to explore the common disease rare variant hypothesis. Recently, we have proposed an approach named Logistic Bayesian LASSO (LBL) to identify association with rare haplotypes in a case-control setting. LBL is an adaptation of the Bayesian counterpart of penalized regression approach LASSO. Our approach is able to weed out unassociated (especially common) haplotypes to achieve enough noise reduction so that the signals contained in the associated rare haplotypes can be more easily detected. Using LBL, we were able to implicate a specific rare haplotype for Age-related Macular Degeneration (AMD) in the Complement Factor H (CFH) gene for the first time. In addition to rare variants, gene-environment interaction (GXE) is believed to be another important contributor to missing heritability. LBL has a flexible framework that can incorporate non-genetic (environmental) covariates and gene- environment interactions. In this project we propose methods for exploring interactions between rare haplotypes and environmental factors in cancer epidemiology, rst in the setting of simple random sampling and then for stratified random sampling. We will develop methods both with and without the assumption of gene-environment independence. The methods will be extensively studied through simulations under a variety of settings. They will be applied to several cancer datasets available from NIH's database of Genotypes and Phenotypes (dbGaP) and the AMD data. Further, the method for stratified sampling will be used to analyze the NCI-sponsored Kidney Cancer Case-Control Study, wherein the controls were selected by stratified sampling using frequency matching with cases. We will implement the proposed methods in a well-documented user-friendly software and make it available to the larger scientific community.



Publications

Detecting rare haplotype association with two correlated phenotypes of binary and continuous types.
Authors: Yuan X. , Biswas S. .
Source: Statistics in medicine, 2021-04-15; 40(8), p. 1877-1900.
EPub date: 2021-01-12.
PMID: 33438281
Related Citations

Comparison of haplotype-based tests for detecting gene-environment interactions with rare variants.
Authors: Papachristou C. , Biswas S. .
Source: Briefings in bioinformatics, 2020-05-21; 21(3), p. 851-862.
PMID: 31329820
Related Citations

Bivariate logistic Bayesian LASSO for detecting rare haplotype association with two correlated phenotypes.
Authors: Yuan X. , Biswas S. .
Source: Genetic epidemiology, 2019 12; 43(8), p. 996-1017.
EPub date: 2019-09-23.
PMID: 31544985
Related Citations

A Family-Based Rare Haplotype Association Method for Quantitative Traits.
Authors: Datta A.S. , Lin S. , Biswas S. .
Source: Human heredity, 2018; 83(4), p. 175-195.
EPub date: 2019-02-21.
PMID: 30799419
Related Citations

Logistic Bayesian LASSO for genetic association analysis of data from complex sampling designs.
Authors: Zhang Y. , Hofmann J.N. , Purdue M.P. , Lin S. , Biswas S. .
Source: Journal of human genetics, 2017 Sep; 62(9), p. 819-829.
EPub date: 2017-04-20.
PMID: 28424482
Related Citations

Detecting rare and common haplotype-environment interaction under uncertainty of gene-environment independence assumption.
Authors: Zhang Y. , Lin S. , Biswas S. .
Source: Biometrics, 2017 03; 73(1), p. 344-355.
EPub date: 2016-08-01.
PMID: 27478935
Related Citations

Association of rare haplotypes on ULK4 and MAP4 genes with hypertension.
Authors: Datta A.S. , Zhang Y. , Zhang L. , Biswas S. .
Source: BMC proceedings, 2016; 10(Suppl 7), p. 363-369.
EPub date: 2016-11-15.
PMID: 27980663
Related Citations

Kullback-Leibler divergence for detection of rare haplotype common disease association.
Authors: Lin S. .
Source: European journal of human genetics : EJHG, 2015 Nov; 23(11), p. 1558-65.
EPub date: 2015-03-04.
PMID: 25735482
Related Citations

Detecting associations of rare variants with common diseases: collapsing or haplotyping?
Authors: Wang M. , Lin S. .
Source: Briefings in bioinformatics, 2015 Sep; 16(5), p. 759-68.
EPub date: 2015-01-17.
PMID: 25596401
Related Citations

An Improved Version of Logistic Bayesian LASSO for Detecting Rare Haplotype-Environment Interactions with Application to Lung Cancer.
Authors: Zhang Y. , Biswas S. .
Source: Cancer informatics, 2015; 14(Suppl 2), p. 11-6.
EPub date: 2015-02-09.
PMID: 25733797
Related Citations

FamLBL: detecting rare haplotype disease association based on common SNPs using case-parent triads.
Authors: Wang M. , Lin S. .
Source: Bioinformatics (Oxford, England), 2014-09-15; 30(18), p. 2611-8.
EPub date: 2014-05-21.
PMID: 24849576
Related Citations

Population-based association and gene by environment interactions in Genetic Analysis Workshop 18.
Authors: Satten G.A. , Biswas S. , Papachristou C. , Turkmen A. , K├Ânig I.R. .
Source: Genetic epidemiology, 2014 Sep; 38 Suppl 1, p. S49-56.
PMID: 25112188
Related Citations

Evaluation of logistic Bayesian LASSO for identifying association with rare haplotypes.
Authors: Biswas S. , Papachristou C. .
Source: BMC proceedings, 2014; 8(Suppl 1), p. S54.
EPub date: 2014-06-17.
PMID: 25519334
Related Citations

Detecting rare haplotype-environment interaction with logistic Bayesian LASSO.
Authors: Biswas S. , Xia S. , Lin S. .
Source: Genetic epidemiology, 2014 Jan; 38(1), p. 31-41.
EPub date: 2013-11-23.
PMID: 24272913
Related Citations




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