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Publication Information
Affiliation
Division of Pediatric Gastroenterology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, 1760 Haygood Drive, W-427, Atlanta, GA, 30322, USA.; Division of Pediatric Gastroenterology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, 1760 Haygood Drive, W-427, Atlanta, GA, 30322, USA.; Division of Pediatric Gastroenterology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, 1760 Haygood Drive, W-427, Atlanta, GA, 30322, USA.; Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, USA.; Division of Digestive Diseases, Hepatology, and Nutrition, Connecticut Children's Medical Center, Hartford, CT, USA.; Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; Section of Pediatric Gastroenterology, Texas Children's Hospital Baylor College of Medicine, Houston, TX, USA.; Center for Integrative Genomics, Georgia Institute of Technology, Atlanta, GA, USA.; Department of Human Genetics, Emory University, Atlanta, GA, USA.; Department of Human Genetics, Emory University, Atlanta, GA, USA.; Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, USA.; Division of Pediatric Gastroenterology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, 1760 Haygood Drive, W-427, Atlanta, GA, 30322, USA. skugath@emory.edu.
Authors
Venkateswaran Suresh, Somineni Hari K, Matthews Jason D, Kilaru Varun, Hyams Jeffrey S, Denson Lee A, Kellamayer Richard, Gibson Greg, Cutler David J, Conneely Karen N, Smith Alicia K, Kugathasan Subra
Studies
Abstract
In peripheral blood, DNA methylation (DNAm) patterns in inflammatory bowel disease patients reflect inflammatory status rather than disease status. Here, we examined DNAm in diseased rectal mucosa from ulcerative colitis (UC) patients, focusing on constituent cell types with the goal of identifying therapeutic targets for UC other than the immune system. We profiled DNAm of rectal mucosal biopsies of pediatric UC at diagnosis (n = 211) and non-IBD control (n = 85) patients and performed epigenome-wide association studies (EWAS) of specific cell types to understand DNAm changes in epithelial, immune and fibroblast cells across disease states, course, and clinical outcomes. We also examined longitudinal analysis on follow-up samples (n = 73), and comparisons were made among patients with clinical outcomes including those undergoing colectomy versus those who did not. Additionally, we included RNA-seq from the same subjects to assess the impact of CpG sites on the transcription of nearby genes during the disease course.