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Understanding heterogeneity and interaction in the context of whole genome genetic analysis

Balu, Sriram (2007) Understanding heterogeneity and interaction in the context of whole genome genetic analysis. Master's Thesis, University of Pittsburgh. (Unpublished)

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Interactions and heterogeneity play a vital role in the miscommunication between genotype and phenotype in complex diseases. Detection of genes that influence the risk of common, complex disorders involves many statistical and computational challenges. This led us to investigate and compare the common methods of linkage analysis in complex diseases. We applied various methods of linkage analysis on the simulated dataset from the Genetic Analysis Workshop (GAW) 14. As the disease modeled in this dataset resembled a qualitative disorder, we employed methods such as nonparametric linkage scans, association studies of susceptibility regions, and conditional studies (conditioning on a previously identified susceptibility locus). The goal of this project was to study the efficiencies and inadequacies of various methods in detecting interactions and heterogeneity in the simulated dataset.The methods used on this dataset showed very low percentage in the detection of interactions. We attribute this unsatisfactory performance of these methods mostly to the low prevalence of interactions in the imaginary populations studied. We also propose various ways of improving the power in these analyses like considering haplotype studies instead of targeting single markers and increasing the range of the flanking markers around regions of high LOD scores.Public Health Importance: Understanding the complexities involved in the genetics of diseases will provide new insight for disease prevention and health promotion. For over twenty years, public health agencies have focused more and more on newborn screening programs to detect and prevent rare genetic disorders. But common complex disorders pose a bigger problem because of their unique characteristics like heterogeneity, gene-gene interactions, multiple susceptible loci, incomplete penetrance, phenocopy and presence of environmental risk factors. By comparing common methods of linkage analysis in complex disorders in the simulated dataset of Genetic Analysis Workshop (GAW) 14, our study aims to come up with a better understanding of how heterogeneity and interaction work in the context of a whole genome genetic analysis. It is also expected to lay a foundation on which future public health researchers will be able to expand on our work.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairBarmada, Michael Mmichael.barmada@hgen.pitt.eduBARMADA
Committee MemberFeingold, Eleanoreleanor.feingold@hgen.pitt.eduFEINGOLD
Committee MemberWilson, John Wwilson@nsabp.pitt.eduJWW
Date: 21 June 2007
Date Type: Completion
Defense Date: 30 January 2007
Approval Date: 21 June 2007
Submission Date: 28 March 2007
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Human Genetics
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: association studies; conditional analysis; gene-gene interaction; genetic heterogeneity; genomescan; heterogeneity; interaction; linkage analysis; logistic regression; nonparametric linkage analysis; parametric linkage analysis; phenocopy; polygenic inheritance; redefinition; stratification; TDT analysis; weighted analysis; complex diseases; incomplete penetrance
Other ID:, etd-03282007-231904
Date Deposited: 10 Nov 2011 19:33
Last Modified: 15 Nov 2016 13:37


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