The IBDGC has two primary responsibilities:
- Manage a repository of Crohn’s disease and ulcerative colitis biospecimen for use by Consortium members and the larger scientific community
- Conduct genetic analyses to identify genes and loci associated with Inflammatory Bowel Disease
We are involved with several independent genetic research studies and actively work with members of the IBD clinical and genetics communities on collaborative projects. Our studies utilize DNA and other biospecimens from patients affected with Inflammatory Bowel Disease and healthy controls. Genetic information is analyzed as we strive to identify and better understand the way in which IBD manifests and how certain genetic traits contribute to this manifestation.
The next phase for advancing IBD research will focus on collaborative, multi-disciplinary studies, to elucidate the mechanisms whereby risk-conferring genetic variants influence IBD pathophysiology.
The NIDDK Inflammatory Bowel Disease Genetics Consortium (IBDGC) was created to advance genetic research on Crohn’s Disease and Ulcerative Colitis. The overall objective of the Consortium is to identify genes or genomic regions that are associated with increased risk of IBD and with specific phenotypic manifestations. The Consortium has maintained the initial structure of 6 Genetic Research Centers (GRCs) and a Data Coordinating Center (DCC).
Phase 1 - Grant Cycle 2002-2007 The IBD Genetics Consortium was started in 2002 by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). During the first 5 year funding cycle collections included blood for DNA isolation and lymphoblastoid cell lines, and clinical phenotype data for affected independent cases, affected families, and probands with unaffected family controls. We also established a standard phenotyping manual and forms for IBD. Our Genome Wide Association Studies (GWAS) were instrumental in identifying top CD associated loci, specifically NOD2, IL23R and ATG16L1.
- Major Publications:
- Duerr et al., Science 2006
- Rioux et al., Nature Genetics 2007
Phase 2 - Grant Cycle 2007-2012 During phase 2 collections evolved with the recent genetic findings to focus primarily on independent cases, and population controls. We continued to collect blood for DNA isolation and lymphoblastoid cell lines, and added serum collections. During this time we joined the International IBDGC for several ground-breaking studies. Our GWAS studies were instrumental in identifying the top CD and UC associated loci, and have contributed greatly to several meta-analyses and, specific to CD and UC. These findings allowed us to collaborate with the auto-immune diseases community to design the ImmunoChip (iChip). With a combined total of over 75,000 subjects (IBD cases and controls) the total IBD associated loci to meet genome-wide significance was brought to 163. In addition we learned that many of these loci overlap with other auto-immune diseases, and mycobacterial infection.
- Major Publications:
- McGovern et al., Nature Genetics 2010
- Rivas et al., Nature Genetics 2011
- Jostins et al., Nature 2012
Phase 3 - Grant Cycle 2012-2017 For the current funding period we are adding value to the genetic associations with functional studies. This next phase for advancing IBD research is focusing on collaborative, multi-disciplinary studies, has also initiated some projects designed to elucidate the mechanisms whereby risk-conferring genetic variants influence IBD pathophysiology, as we chart the regulation of IBD gene expression. Our current projects were designed to elucidate the mechanisms whereby risk-conferring genetic variants influence IBD pathophysiology. In addition to the previous collections, we are now collecting blood for RNA and PBMCs, surgical intestinal tissue and biopsies, and stool and diet. We are also actively participating in several other IBD consortia. We are continuing to build on previous GWAS studies, with sequencing of additional populations, and more in-depth interrogation of specific loci with functional studies.
- Major Publications:
- Palm et al., Cell 2014
- VanDussen et al., Gastroenterology 2014
- Goyette et al., Nature Genetics 2015
- Liu et al., Nature Genetics 2015 (e-published)
- Cleynen et al., Lancet 2015 (In Press)
- Huang et al., Gastroenterology 2015 (e-published)
The IBDGC is managed by the Data Coordinating Center (DCC):
- Judy H. Cho, MD, Principal Investigator
- Ronald A. Thisted, PhD, PhD, Scientific Director of DCC operations at the University of Chicago
- Phil Schumm, MA, Technical Director of DCC operations at the University of Chicago
- Yashoda Sharma, PhD, Project Administrator
The DCC facilitates scientific interaction among individual Genetic Research Centers (GRCs) through the collection, organization and analysis of study data, especially with the use of common data structures, existing and novel analytic approaches, and testing of interrelated hypotheses.
The IBDGC DCC also serves as the Data Coordinator Center for the International IBD Genetics Consortium.
The IBDGC relies on its member Genetic Research Centers (GRCs) to recruit large numbers of subjects from diverse populations and to leverage the analytic and clinical expertise from their eminent IBD programs. The six GRCs and principal investigators are
- Cedars Sinai Medical Center: Dermot B. P. McGovern, MD, PhD, MRCP
- Icahn School of Medicine at Mount Sinai: Judy H. Cho, MD
- Johns Hopkins University: Steven R. Brant, MD
- University of Montreal: John D. Rioux, PhD
- University of Pittsburgh: Richard H. Duerr, MD
- University of Toronto: Mark Silverberg, MD, PhD, FRCPC
The governance structure of the Consortium has been very effective in making decisions about specific policies, projects and scientific direction. The Steering Committee (SC), chaired by Dr. Judy Cho, makes all major decisions democratically (e.g., use of Consortium samples and DCC funds, project proposals including those from outside the Consortium and ancillary R01 applications, subcommittee structure). The PIs from each GRC serves as voting members. The chair of the analytic subcommittee (Mark Daly), a representative from NIDDK (Robert Karp, Director, Genetics and Genomics Programs of DDDN), the DCC Project Administrator (Yashoda Sharma) and Technical Director of DCC Operations (Phil Schumm) provide additional expertise and also serve as SC members.
Additional Working Groups serving the IBDGC are
- Analytic: Chair, Mark Daly, PhD, Associate Professor of Medicine and Chief of the Analytic and Translational Genetics Unit, Massachusetts General Hospital (MGH)/Harvard Medical School and Senior Associate Member of the Broad Institute. Co-chair, Talin Haritunians, PhD, Genetic Analyst, Cedars Sinai Medical Center.
- Clinical Translation: Dermot McGovern, MD.
- Ancillary Studies Committee: Richard H. Duerr, MD, Dermot B. P. McGovern, MD, PhD, MRCP and Yashoda Sharma, PhD