This is a project to study the genetics of Inflammatory Bowel Disease (IBD) in collaboration with Drs. Steven Brant and Theodore Bayliss of Johns Hopkins University School of Medicine and with the International IBD Consortium. An international consortium of investigators who have previously published genome wide linkage screens for IBD was formed and all members agreed to genotype the same markers in two candidate regions on at least 50 highly informative families with both parents and two or more affected children available for genotyping. These data were then deposited into a common database at the University of Canberra, anonymized and then distributed to the participating groups. Each group performed its own analyses of these data and presented them at a workshop in Australia in 2000. Additional genotyping was performed and a paper was published in the American Journal of Human Genetics that strongly confirmed evidence of one susceptibility locus on chromosome 16 but failed to confirm a second locus on chromosome 12. These analyses led directly to the recent cloning (by two independent members of the consortium) of a gene on chromosome 16 that increases risk for IBD in some families. Currently, the IBD Consortium has finished genotyping the families for additional candidate genes and is analyzing these data and have performed a meta-analysis of published genome wide screens. Dr. Bailey-Wilson is a member of the Analysis committee for this consortium and will continue to interact with Drs. Brant, Bayliss and the IBD Consortium on future analyses of the genetics of IBD. Dr. Bailey-Wilson also is collaborating with Drs. Brant and Bayliss and Dr. Carolien Panhuysen of Boston University on analyses of Dr. Brant's IBD data. Linkage and association studies of genome-wide scan and fine mapping data are ongoing. In this fiscal year, analyses of a candidate locus have yielded evidence of a role for this locus in risk to IBD and a paper has been published on these results. A new collaboration is also being developed by Drs. Brant and Bailey-Wilson with a group of clinicians and other scientists (the Middle Atlantic African American Inflammatory Bowel Disease Study) to allow a concentrated effort to be made to collect families of African American ethnicity who have multiple family members affected with IBD. This has been funded by the NIH and is currently in the data collection stage. Finally, in this fiscal year, Dr. Bailey-Wilson and her graduate student, Betty Doan, have worked with Dr. Brant to type markers in additional candidate regions and to analyze these data for linkage and association analysis, and to also reanalyze Dr. Brant?s data including environmental covariate data. This work is ongoing.
| Karban, Amir S; Okazaki, Toshihiko; Panhuysen, Carolien I M et al. (2004) Functional annotation of a novel NFKB1 promoter polymorphism that increases risk for ulcerative colitis. Hum Mol Genet 13:35-45 |
| Brant, S R; Panhuysen, C I; Bailey-Wilson, J E et al. (2000) Linkage heterogeneity for the IBD1 locus in Crohn's disease pedigrees by disease onset and severity. Gastroenterology 119:1483-90 |
