Evidence map›Paper›PMID 30779925›Full record

ArticleGastroenterology2019

Blood-Derived DNA Methylation Signatures of Crohn's Disease and Severity of Intestinal Inflammation.

Hari K Somineni, Suresh Venkateswaran, Varun Kilaru, Urko M Marigorta, Angela Mo, David T Okou, Richard Kellermayer, Kajari Mondal, Dawayland Cobb, Thomas D Walters and 19 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Gastroenterology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed, 3 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

95 citing papers in PubMed, 3 syntheses or guidelines pooled it.

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35 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

29 authors.

Hari K SomineniGenetics and Molecular Biology Program, Emory University, Atlanta, Georgia; Division of Pediatric Gastroenterology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia.
Suresh VenkateswaranDivision of Pediatric Gastroenterology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia.
Varun KilaruDepartment of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia.
Urko M MarigortaCenter for Integrative Genomics, Georgia Institute of Technology, Atlanta, Georgia.
Angela MoCenter for Integrative Genomics, Georgia Institute of Technology, Atlanta, Georgia.
David T OkouDivision of Pediatric Gastroenterology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia.
Richard KellermayerSection of Pediatric Gastroenterology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas.
Kajari MondalDivision of Pediatric Gastroenterology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia.
Dawayland CobbDepartment of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia.
Thomas D WaltersDivision of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Anne GriffithsDivision of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Joshua D NoeDepartment of Pediatric Gastroenterology, Hepatology and Nutrition, Medical College of Wisconsin, Milwaukee, Wisconsin.
Wallace V CrandallDivision of Pediatric Gastroenterology, Nationwide Children's Hospital, Ohio State University College of Medicine, Columbus, Ohio.
Joel R RoshDepartment of Pediatrics, Goryeb Children's Hospital, Morristown, New Jersey.
David R MackDepartment of Pediatrics, Children's Hospital of Eastern Ontario IBD Centre and University of Ottawa, Ottawa, Ontario, Canada.
Melvin B HeymanDepartment of Pediatrics, University of California, San Francisco, San Francisco, California.
Susan S BakerDepartment of Digestive Diseases and Nutrition Center, University at Buffalo, Buffalo, New York.
Michael C StephensDepartment of Pediatric Gastroenterology, Mayo Clinic, Rochester, Minnesota.
Robert N BaldassanoDepartment of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania.
James F MarkowitzDepartment of Pediatrics, Northwell Health, New York, New York.
Marla C DubinskyDepartment of Pediatrics, Mount Sinai Hospital, New York, New York.
Judy ChoDepartment of Pediatrics, Mount Sinai Hospital, New York, New York.
Jeffrey S HyamsDivision of Digestive Diseases, Hepatology, and Nutrition, Connecticut Children's Medical Center, Hartford, Connecticut.
Lee A DensonDivision of Pediatric Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Greg GibsonCenter for Integrative Genomics, Georgia Institute of Technology, Atlanta, Georgia.
David J CutlerDepartment of Human Genetics, Emory University, Atlanta, Georgia.
Karen N ConneelyGenetics and Molecular Biology Program, Emory University, Atlanta, Georgia; Department of Human Genetics, Emory University, Atlanta, Georgia.
Alicia K SmithGenetics and Molecular Biology Program, Emory University, Atlanta, Georgia; Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia; Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia.
Subra KugathasanGenetics and Molecular Biology Program, Emory University, Atlanta, Georgia; Division of Pediatric Gastroenterology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia; Department of Human Genetics, Emory University, Atlanta, Georgia. Electronic address: skugath@emory.edu.

Funding

Stem Cell/Organoid and Genome Editing CoreP30DK078392 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI Alexander Miethke · 2007 to 2026
$24.4M
Gene discoveries in subjects with Crohn's disease of African descentR01DK087694 · NIDDK · EMORY UNIVERSITY · PI KUGATHASAN, SUBRA · 2011 to 2023
$10.3M
Causes and consequences of neutrophil dysfunction in early onset Crohn's diseaseR01DK098231 · NIDDK · EMORY UNIVERSITY · PI DENSON, LEE ARMISTEAD, KUGATHASAN, SUBRA · 2013 to 2017
$3.3M
New computational, transcriptional, and genome editing approaches to the biology of inflammatory bowel diseaseR01DK119991 · NIDDK · GEORGIA INSTITUTE OF TECHNOLOGY · PI GIBSON, GREGORY C · 2018 to 2021
$692k
NIDDK NIH HHS P30 DK078392NIDDK NIH HHS R01 DK087694NIDDK NIH HHS R01 DK098231NIDDK NIH HHS R01 DK119991
6 · The paper itself

Abstract

BACKGROUND &

aimsCrohn's disease is a relapsing and remitting inflammatory disorder with a variable clinical course. Although most patients present with an inflammatory phenotype (B1), approximately 20% of patients rapidly progress to complicated disease, which includes stricturing (B2), within 5 years. We analyzed DNA methylation patterns in blood samples of pediatric patients with Crohn's disease at diagnosis and later time points to identify changes that associate with and might contribute to disease development and progression.

methodsWe obtained blood samples from 164 pediatric patients (1-17 years old) with Crohn's disease (B1 or B2) who participated in a North American study and were followed for 5 years. Participants without intestinal inflammation or symptoms served as controls (n = 74). DNA methylation patterns were analyzed in samples collected at time of diagnosis and 1-3 years later at approximately 850,000 sites. We used genetic association and the concept of Mendelian randomization to identify changes in DNA methylation patterns that might contribute to the development of or result from Crohn's disease.

resultsWe identified 1189 5'-cytosine-phosphate-guanosine-3' (CpG) sites that were differentially methylated between patients with Crohn's disease (at diagnosis) and controls. Methylation changes at these sites correlated with plasma levels of C-reactive protein. A comparison of methylation profiles of DNA collected at diagnosis of Crohn's disease vs during the follow-up period showed that, during treatment, alterations identified in methylation profiles at the time of diagnosis of Crohn's disease more closely resembled patterns observed in controls, irrespective of disease progression to B2. We identified methylation changes at 3 CpG sites that might contribute to the development of Crohn's disease. Most CpG methylation changes associated with Crohn's disease disappeared with treatment of inflammation and might be a result of Crohn's disease.

conclusionsMethylation patterns observed in blood samples from patients with Crohn's disease accompany acute inflammation; with treatment, these change to resemble methylation patterns observed in patients without intestinal inflammation. These findings indicate that Crohn's disease-associated patterns of DNA methylation observed in blood samples are a result of the inflammatory features of the disease and are less likely to contribute to disease development or progression.

Indexed as

Genome-Wide Association StudyAdolescentAge FactorsCase-Control StudiesChildChild, PreschoolCrohn DiseaseDisease ProgressionDNA MethylationFemaleFollow-Up StudiesGene Expression RegulationGenotypeHumansInfantInflammationChildrenEpigenetic AlterationInflammatory Bowel DiseaseRisk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn's Disease (RISK) Study

Identifiers

PMID30779925
PMCPMC6529254

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.