- 6/23/23 - 4 forms, 1 itemgroup, 5 items, 1 language
Itemgroup: pht005361
Principal Investigator: Mark Daly, PhD, Massachusetts General Hospital, Boston, MA, USA and The Broad Institute, Cambridge, MA, USA MeSH: Inflammatory Bowel Diseases,Crohn Disease,Colitis, Ulcerative https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001076 The Broad Institute and Massachusetts General Hospital (MGH) are launching a new initiative to perform large-scale exome sequencing in inflammatory bowel disease (Crohn's disease and ulcerative colitis). Given the considerable unmet therapeutic need in inflammatory bowel disease (IBD), the recent emergence of rapid and efficient genome sequencing technologies and the compelling evidence for the role of genetics in these disorders have motivated the founding of a collaborative sequencing effort geared toward the discovery of high-impact genetic variants influencing IBD risk that can serve as guides to future therapeutic development and diagnostic tools. The initiative will be directed by experienced IBD researchers from MGH and the Broad Institute but aims to develop a collaborative exome sequencing network that will partner with researchers worldwide. Two large pilot exome sequencing projects are being launched immediately as part of this initiative based on established genetic study designs that enrich for the discovery of rare, high-impact risk and protective variants. *1) Early-onset pediatric IBD:* a major focus of the work will surround full-exome sequencing of the earliest-onset childhood IBD cases. It has long been recognized in many diseases that penetrant genetic risk factors are much more likely to be found in cases with unusually early onset. The Broad Institute has completed more than 50,000 exomes in the past two years; and their technical expertise in generating and processing such sequencing data, along with population genetic variation patterns from these experiments, will provide a foundation for obtaining the best outcome in the interpretation of these cases. Samples with IBD onset before 6 years of age - and in some cases going up to age 10 - collected by IBD researchers around the world are welcomed for inclusion in this study. *2) Adult-onset IBD case-control study:* Genetic mapping has provided dramatic insights into IBD pathogenesis in recent years, but a substantial amount of heritability - in particular the role of strong-acting rare mutations - is yet to be elucidated. To deliver those insights, IBD cases with an unusually low burden of known genetic risk factors (particularly emphasizing those with positive family history and/or from isolated or enriched populations) will be contrasted with population controls that have an extremely high burden of known IBD risk factors, enhancing discovery of critical protective variants that may provide the best clues for therapeutic development. This project will also be initiated as an international collaboration, particularly among researchers with sample sets with Immunochip genotyping that will enable the immediate genetic identification of these enriched target populations. This project will be supported by the NHGRI Large-Scale Sequencing Program, with all generated data made publicly available to the research community through standard NIH databases.

pht005362.v1.p1

1 itemgroup 3 items

pht005363.v1.p1

1 itemgroup 3 items

pht005364.v1.p1

1 itemgroup 6 items
- 12/12/22 - 4 forms, 1 itemgroup, 2 items, 1 language
Itemgroup: IG.elig
Principal Investigator: Judy Cho, MD, Department of Medicine, Yale University, New Haven, CT, USA MeSH: Colitis, Ulcerative,Inflammatory Bowel Diseases https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000345 This dataset contains data for 1,028 white, non-Hispanic, European ancestry individuals with ulcerative colitis who were included in a genome-wide association study published by Silverberg et al. (2009). These individuals were ascertained in North America and selected to have either left-sided or extensive disease (i.e., individuals with proctitis only were excluded). Genotyping was performed using the Illumina HumanHap300v2 (n = 540) and HumanHap550v3 (n = 488) Genotyping BeadChips at the Feinstein Institute for Medical Research. Control data (not included) were obtained from the NIDDK IBD Genetics Consortium's Crohn's Disease GWAS (available from dbGaP) and from studies 64 and 65 deposited in the Illumina iControlDB. Seven hundred eighty individuals in this dataset were taken from the NIDDK IBD Genetics Consortium cell line repository (http://www.niddkrepository.org). These individuals are identified in the file dbGaP_SubjectDS.txt. The subject IDs for these individuals may be used to request corresponding samples for follow-up research through the repository. In addition, complete phenotype data for these individuals are included, collected using the Consortium's forms and phenotyping manual (both included). The remaining 248 individuals were identified from pre-existing collections ascertained by members of the Consortium or their collaborators. For these samples, several of the items in the phenotype file are incomplete. Those who wish to replicate the results in Silverberg et al. should note that 6 individuals with missing genotype rates 0.07 were excluded from that analysis (leaving 1,022 affected samples total). In addition, the minor allele frequencies (MAFs) reported in the publication were calculated using only those individuals who were included in the allelic association tests (n = 977 for SNPs included in the HumanHap300 and n = 476 for SNPs included only in the HumanHap550). These tests were performed using conditional logistic regression on gender-ancestry strata; individuals who were not placed in a stratum (using the procedure described in the supplementary information for Silverberg et al.) were excluded. The indicator variables hh300 and hh550 in the file dbGaP_PhenotypeDS.txt identify the samples included in the allelic association tests, and may be used to replicate the published MAFs among affected individuals.

pht002374.v1.p1

1 itemgroup 5 items

pht002375.v1.p1

1 itemgroup 2 items

pht002376.v1.p1

1 itemgroup 60 items
- 10/12/22 - 5 forms, 1 itemgroup, 5 items, 1 language
Itemgroup: pht001279
Principal Investigator: Vincent Young, MD PhD, University of Michigan, Ann Arbor, MI, USA MeSH: Pouchitis,Inflammatory Bowel Diseases,Colitis, Ulcerative https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000262 The aims of the multi-center Ulcerative Colitis Human Microbiome Project (UCHMP) are to examine the role of the enteric microbiome in causing human ulcerative colitis, specifically the development of pouchitis. Pouchitis is an inflammatory condition of the surgically-created ileoanal pouch that serves as a pseudo-rectum in patients with ulcerative colitis who have undergone a total colectomy. It is a condition unique to ulcerative colitis (UC), as it rarely occurs in non-UC patients who have the same procedure. Within one year, about 50% of patients will develop pouchitis. The condition is almost certainly due to aspects of the pouch microbiota on a background of genetic susceptibility, as most patients respond to treatment with antibiotics. While there have been reports on the microbiota in pouchitis patients, all have been performed after the inflammatory process is initiated, rendering interpretation of the results difficult, as the inflammatory process itself will change the microbiota. *Our project is therefore unique and possibly the only opportunity in the role of the enteric microbiome in IBD in a prospective manner, thereby establishing potentially important causal relationships between microbiota structure or function and development of UC.*The studies also offer two additional advantages. First, the development of the pouch microbiota can be observed prospectively. Second, the cause of antibiotic treatment failure in some patients with pouchitis may be revealed. The two aims are (1) to identify causal factors in the structure and/or function of the enteric microbiota in the development of pouchitis, and (2) to determine the basis of treatment failure in UC pouchitis patients. Our analyses will include serial measurements of enteric microbial structure (16S rRNA gene-based), function (metagenomics and functional candidate genes), and cultivation, the latter to enhance interpretation of gene sequences derived from metagenomes and targeted gene surveys (either functional or 16S genes). The insights gained from these studies will help us understand the fundamental and causative roles of the enteric microbiome in human inflammatory bowel diseases (IBD). This information will be the basis for developing strategies to restore host-microbial relationships to prevent and treat IBD.

pht001280.v3.p2

1 itemgroup 5 items

Eligibility

1 itemgroup 9 items

pht006261.v1.p2

1 itemgroup 6 items

pht006262.v1.p2

1 itemgroup 10 items
- 10/12/22 - 6 forms, 1 itemgroup, 4 items, 1 language
Itemgroup: IG.elig

pht003260.v1.p1

1 itemgroup 4 items

pht003261.v1.p1

1 itemgroup 5 items

pht003262.v1.p1

1 itemgroup 5 items

pht003263.v1.p1

1 itemgroup 5 items

pht003264.v1.p1

1 itemgroup 6 items

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