This proposal describes the development of a Data Coordinating Center (DCC) at the University of Chicago. Progress in defining the pathogenesis of inflammatory bowel disease (IBD) through genetic approaches will be accelerated greatly through the establishment of an IBD Genetics Consortium. This proposal outlines a data coordinating center (DCC) at the University of Chicago. The overall objective of the IBD Genetics Consortium will be the identification of genes or genomic regions that are associated with increased risk of IBD and with specific phenotypic manifestations.
Specific Aim I. To identify and implement IBD genetics projects which can most efficiently be completed through a Consortium structure. The specific objectives of the Consortium will be established through the Steering and Planning Committee and will reflect the nature of the studies proposed through individual Genetic Research Center (GRC) applications. It is expected that the DCC will play a key role in the planning, development and implementation of Consortium objectives. Potential joint issues include: mega-analysis of completed genomewide searches, stratified analysis of genome wide data based on established associations, support of positional gene identification efforts, candidate gene studies, and acquisition of data on clinical covariates, such as tobacco use, age of onset, and disease location.
Specific Aim II. To perform the functions of a data coordinating center and genetic analysis center. Functional specifications of the DCC are described. In particular, careful development of a study protocol and Manual of Procedures will be the initial task of the Consortium, to be developed by the DCC with iterative input from the Steering and Planning Committee and individual GRCs. The use of both existing and novel methods of genetic analysis is proposed. Prior experiences in collaborative genomewide screens have been critical in advancing understanding of the challenges associated with pooling genomewide linkage data. These key concepts have been incorporated into the proposed mega-analysis. Methods to reduce genetic heterogeneity are proposed through stratified analyses based on established gene associations, locus-locus and gene-environment interactions.
Specific Aim III. To collect common patient specimens and facilitate common genotyping requirements. The creation and maintenance of a DNA and cell line repository at the Coriell Institute containing appropriate patient and control samples is proposed. Provisions for common genotyping are described, if so requested by the Steering Committee or individual GRCs.
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