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Methods for family-based designs in genetic epidemiology studies

Carlson, Jenna C. (2017) Methods for family-based designs in genetic epidemiology studies. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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In genetic epidemiology studies of complex traits, there are two main design types through which we can study complex traits. The first is population-based, in which independent cases and controls are collected to assess the difference in the underlying genetic makeup between affected and unaffected individuals. The other is family-based, in which data from families with at least one affected individual are collected. This allows for the study of the transmission of genetic variants between parent and offspring and how genetic variants differ between the affected individual(s) and the unaffected individuals within a family.
We examine two hallmarks of complex traits in this dissertation. The first is the combination of mixed data types into a single likelihood, leveraging assumptions about the genotype frequencies to the extent that the data support them. To do this we will employ an empirical Bayes-type shrinkage estimation approach. Combining multiple data structures into a robust joint analysis may provide additional information about the disease loci driving complex traits. Secondly, we will examine heterogeneous presentation of traits associated with complex disorders. This phenotypic heterogeneity may arise due to genetic underpinnings, different environmental exposures, or perhaps by unknown factors. Specifically, we will address the following questions: (1) How can family data be combined with case-control data from the same study to improve estimates of disease association in a way that is robust to model misspecification? (2) How can genetic sources of phenotypic heterogeneity be identified in case-control and family-based studies?
The public health significance of this research is that these methods will further under-standing of the genetic architecture and will provide framework for studying other complex traits. Knowing the underlying genetic structure of a complex disease like orofacial clefting will aid in identifying any possible modifiable environmental factors that may also be contributing to the etiology of the disease. In order to identify those factors, we must have foundational knowledge of the biologic mechanism through which OFCs arise.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Carlson, Jenna C.jnc35@pitt.edujnc350000-0001-5483-0833
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairFeingold, Eleanorfeingold@pitt.edufeingold
Committee MemberLeslie, Elizabeth J.ejl40@pitt.eduejl40
Committee MemberAnderson, Stewart J.sja@pitt.edusja
Committee MemberChen,
Committee MemberArena, Vincentarena@pitt.eduarena
Date: 29 June 2017
Date Type: Publication
Defense Date: 20 March 2017
Approval Date: 29 June 2017
Submission Date: 30 March 2017
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 124
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Biostatistics
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: genome-wide association study, empirical Bayes-type estimation, shrinkage estimation, phenotypic heterogeneity, complex traits
Date Deposited: 29 Jun 2017 23:38
Last Modified: 01 May 2019 05:15


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