PROGRESS: PSC Resource of Genetic Risk, Environment, and Synergy Studies

Primary sclerosing cholangitis (PSC) is a progressive liver disease strongly associated with inflammatory bowel disease (IBD). About 75% of PSC patients are diagnosed with IBD, most commonly ulcerative colitis (UC) and conversely, 5-7% of IBD patients develop PSC.

Identification of Disease Genes for Significant Linkage Regions Identified in NIDDK IBD Genetics Consortium SNP Linkage Scan

Crohn’s disease (CD) is a complex genetic disorder of chronic inflammation of the gastrointestinal tract that results in increased morbidity, mortality, risk of cancer and cost to patient and society. Twenty to 30% of patients have a CD family history and the disease is four-fold increased in persons of Ashkenazi Jewish (AJ) ancestry.

Gene Discoveries in Subjects With Crohn’s Disease of African Descent

Crohn’s disease (CD) is heritable. Most genetic discovery to date has been performed in Caucasians of European descent. African Americans (AAs) endure a similar disease burden as Caucasians, yet less than 1% of research, publications, or clinical trials have focused on AA with CD.

Crohn’s Disease: Influence of Host Genetics on the Composition and Function of the Gut Microbial Communities

The interplay between a host’s genetics, immune system, and intestinal microbial communities is a dynamic force influencing health and disease status. This proposal will assess how genetic variants associated with IBD shape the microbiota and the functional consequences that alter host responses and culminate pathologic inflammation.

Integrative Genetic and Genomic Analyses in the Inflammatory Bowel Disease

The inflammatory bowel diseases (IBD), composed of Crohn’s disease (CD) and ulcerative colitis (UC), result from an inappropriately directed inflammatory response to the enteric microbiota in a genetically susceptible host. Genome wide association studies (GWAS) have linked 163 specific single nucleotide polymorphisms (SNPs) to IBD disease pathogenesis.

Defining of Crohn's Disease Subtypes Using Genetics and Metagenomics

Crohn disease (CD) is a complex disease involving both genetic and environmental factors. We propose that a specific form of CD can be defined based on Paneth cell function. Of the 150 susceptibility alleles that are associated with this disease, we have previously identified two genes with coding mutations that are associated with abnormal Paneth cell function.

A Genetic Model of Inflammatory Bowel Disease Using Human Intestinal Organoids

Inflammatory bowel disease (IBD) refers to a spectrum of genetic and phenotypically complex disorders that are thought to result from dysregulated immune responses to commensal microbes in genetically susceptible hosts. In IBD, the intestinal epithelium is characterized by increased permeability both in active disease and remission states, and increased permeability has been associated with elevated risk of relapse, yet the precise mechanisms remain undefined.

Defining the Genetic Architecture of IBD in Ashkenazi Jewish Populations

The inflammatory bowel diseases (IBD) are comprised of Crohn’s disease and ulcerative colitis and affect approximately 1.4 million Americans. A central feature of IBD epidemiology is the 4.3-7.7 fold increased prevalence of disease in Ashkenazi Jewish populations.

Functional Outcomes of Common and Rare IBD Associated Variants

The interplay between microbial and genetic susceptibility factors is central to the development of inflammatory bowel disease (IBD). Innate mechanisms, in particular through pattern recognition receptor (PRR) pathways, are the initiating drivers of host responses to microbes.

Innate Immune Pathways and the Microbiome in Hispanics With Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a common and devastating immune-mediated disease in which the mucosal immune system abnormally recognizes the intestinal bacterial flora leading to chronic inflammation. The causes of IBD may lie in the interplay between host response genes and a microbiome with pathogenic properties.

Using Human Intestinal Organoids to Model IBD Pathogenesis

Inflammatory bowel disease (IBD) is a chronic disease characterized by intermittent episodes of intestinal inflammation and disruption of the intestinal epithelial barrier. The IBD Genetics Consortium has intensively studied the genetic architecture of this complex disease.

Differential Impact of Smoking on Trancsriptome and Epigenome in Crohn's Disease and Ulcerative Colitis

Biomarking IBD Patient Specific Disease Features Using the Epithelial Antigenic Petidome

In immune-mediated diseases such as type1 diabetes, target-cell autoantibodies have emerged as important clinical biomarkers of pre-clinical disease progression and mechanistic disease subsets. However, with the focus on genetics, inflammatory effectors, and microbiome, there has not been a modern search for such antibody biomarkers and the potential contribution of anti-epithelial autoimmunity in IBD.

Leveraging the Epigenome of Inflammatory Bowel Disease to Gain Mechanistic Insights Into Disease Pathophysiology

Ulcerative colitis (UC) is a chronic relapsing and remitting intestinal inflammatory disorder with a very heterogeneous clinical course. While on life-long maintenance therapy, although most patients achieve complete mucosal healing with no disease activity during the course of treatment of UC, a subgroup (~40%) experience chronically active severe disease with persistent inflammation as reflected by need for escalation of medical therapy or surgery.

Profiling Intraepithelial Lymphocyte Populations in Health and Crohn’s Disease

Immunological surveillance at barrier surfaces is essential to provide defense against enteric pathogens and maintain mucosal homeostasis. Disruption of the balance between pro-inflammatory and regulatory immune response can lead to a loss of mucosal tolerance and development of chronic inflammatory disease, such as Crohn’s disease (CD).

Role of Cytomegalovirus in the Natural History of Crohn’s Disease

Crohn’s disease (CD) is a multifactorial and complex disease, orchestrated by several genetic and environmental triggers. The best known genetic marker for CD is the nucleotide oligomerization domain 2 (NOD2), a cytoplasmic receptor that responds to bacterial pathogens.

Identifying Population Specific IBD Associated Mutations, Genes and Pathways

Inflammatory bowel disease (IBD) is a group of disorders that involve chronic inflammation of the colon and small intestine. The two major types of IBD are ulcerative colitis (UC): long term inflammation and ulcers of the colon and rectum, and Crohn’s Disease (CD): inflammation of the digestive tract lining that can spread into affected tissues.

Functional Molecular Investigation of Inflammatory Bowel Disease (IBD) Risk Variants

Inflammatory bowel disease (IBD) is a chronic disease characterized by intermittent episodes of intestinal inflammation and disruption of the intestinal epithelial barrier. The IBD Genetics Consortium has intensively studied the genetic architecture of this complex disease.

Understanding How a Loss of Epigenetic Reader SP140 Contributes to IBD

Genetics underlie susceptibility to inflammatory bowel disease (IBD) but the rapid rise in incidence, as well as low concordance rates, point to a prevalent role for the environment and possibly the epigenome.

New Computational, Transcriptional, and Genome Editing Approaches to the Biology of Inflammatory Bowel Disease

Over the past decade, the NIDDK IBDGC (Inflammatory Bowel Disease Genetics Consortium) has generated extraordinary datasets in support of genetic analysis of the onset, progression, and therapeutic response to Crohn’s disease and ulcerative colitis.