Power Analysis and Extension of a Robust Test of Linkage and Association of Human Complex Disease Genes

The main focus of this work is a modern approach for gene mapping of complex human diseases, the Transmission/Disequilibrium Test (TDT). My studies demonstrate that the TDT is a robust, nuclear family based analysis that can test linkage in the presence of association. I show the advantages and disadvantages of the TDT in the current application of gene mapping and the reason that association study such as the TDT is considered to be the future of genetic studies of complex human diseases. Power analysis, a powerful tool to investigate and improve the TDT, has been extensively developed in recent years. However, previous investigations are either inaccurate or not generally applicable. I propose an approach that is the most accurate and general way to compute the power of the TDT. Its applications were examined and are discussed. This approach has been implemented in a user-friendly computer program — TDT Power Calculator. All of the results presented in this thesis were generated by this program with ease. The approach and the program developed here are a significant advance for theoreticians to accurately investigate the statistical power of the TDT in various situations. The program should also be important for empirical geneticists to accurately and efficiently plan studies using the TDT for their special situations. Finally, I developed and investigated an extension of the TDT, in which unaffected children were employed. In some realistic situations, when the disease prevalence is relatively large, this extension may be more powerful than the classical TDT.

Grantor dc:publisher

Creighton University

Year dc:date.issued

2000

Author dc:creator

• Chen, Wei-Min

Advisor dc:contributor.advisor

• Deng, Hong-Wen

Statement dc:rights

• Copyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above.

Language dc:language.iso

en_US

Handle dc:identifier.uri

http://hdl.handle.net/10504/65400

OAI identifier oai:identifier

oai:cdr.creighton.edu:10504/65400