Finding the genetic determinants of common complex disorders is a formidable task, since many genetic and environmental factors, either individually or in combination, influence trait expression. The use of association studies to tackle this challenge is becoming more widespread, especially with the release of the human genome sequence. However, large-scale association studies with sufficient power will be required to find these genes with modest effect sizes. Family-based association studies have consistently been shown to be less powerful than case-control studies, but case-control studies do not efficiently use the data collected for linkage studies and national registries. Therefore, the overall goal of this mentored proposal is to develop and investigate novel study designs and statistical analysis methods for association studies that are a combination of the two aforementioned designs. Specifically, we will: (1) examine sampling strategies for our proposed hybrid design in order to provide guidelines that enable researchers to choose the most informative subjects. (2) derive and evaluate statistical methods to be used for our proposed hybrid design. We will consider methods for stratified analyses, for matched designs, for DNA pooling, and for testing interaction effects. (3) develop and examine statistical methods that correct for population stratification, since our proposed designs may be susceptible to the effects of population stratification. (4) develop user-friendly software that can be used for the design and analysis of our proposed hybrid designs. Additionally, through the planned didactic training in areas including statistical genetics and molecular biology, this mentored proposal will provide me the opportunity to build a strong foundation upon which to build career conducting methodological research involving genetic studies of cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Academic/Teacher Award (ATA) (K07)
Project #
5K07CA094919-04
Application #
6927307
Study Section
Subcommittee G - Education (NCI)
Program Officer
Gorelic, Lester S
Project Start
2002-08-01
Project End
2007-07-31
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
4
Fiscal Year
2005
Total Cost
$137,376
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
Garriock, Holly A; Tanowitz, Michael; Kraft, Jeffrey B et al. (2010) Association of mu-opioid receptor variants and response to citalopram treatment in major depressive disorder. Am J Psychiatry 167:565-73
Shanafelt, Tait D; Bowen, Deborah A; Venkat, Chaya et al. (2009) The physician-patient relationship and quality of life: lessons from chronic lymphocytic leukemia. Leuk Res 33:263-70
Peters, Eric J; Slager, Susan L; Jenkins, Greg D et al. (2009) Resequencing of serotonin-related genes and association of tagging SNPs to citalopram response. Pharmacogenet Genomics 19:1-10
Peters, Eric J; Slager, Susan L; Kraft, Jeffrey B et al. (2008) Pharmacokinetic genes do not influence response or tolerance to citalopram in the STAR*D sample. PLoS One 3:e1872
Palmer, Shanique; Hanson, Curtis A; Zent, Clive S et al. (2008) Prognostic importance of T and NK-cells in a consecutive series of newly diagnosed patients with chronic lymphocytic leukaemia. Br J Haematol 141:607-14
Thurmes, Paul; Call, Timothy; Slager, Susan et al. (2008) Comorbid conditions and survival in unselected, newly diagnosed patients with chronic lymphocytic leukemia. Leuk Lymphoma 49:49-56
Shanafelt, Tait D; Geyer, Susan M; Bone, Nancy D et al. (2008) CD49d expression is an independent predictor of overall survival in patients with chronic lymphocytic leukaemia: a prognostic parameter with therapeutic potential. Br J Haematol 140:537-46
Zent, Clive S; Ding, Wei; Schwager, Susan M et al. (2008) The prognostic significance of cytopenia in chronic lymphocytic leukaemia/small lymphocytic lymphoma. Br J Haematol 141:615-21
Maddocks-Christianson, Kami; Slager, Susan L; Zent, Clive S et al. (2007) Risk factors for development of a second lymphoid malignancy in patients with chronic lymphocytic leukaemia. Br J Haematol 139:398-404
Shanafelt, Tait D; Bowen, Deborah; Venkat, Chaya et al. (2007) Quality of life in chronic lymphocytic leukemia: an international survey of 1482 patients. Br J Haematol 139:255-64

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