ArticleGastroenterology2016
A Frameshift in CSF2RB Predominant Among Ashkenazi Jews Increases Risk for Crohn's Disease and Reduces Monocyte Signaling via GM-CSF.
Open access · greenAbstract read
In one paragraph
Article in Gastroenterology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
9.6field-weighted citation impact, top 2% of its field
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.
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.
Who cites it
40 citing papers in PubMed, 65 citations in OpenAlex.
- Machine Learning-Based Transcriptomic Diagnosis of Periodontitis.International dental journal · 2026Article
- Towards IBD Prediction and Prevention: The Contribution of Genetics and Genomics.Inflammatory bowel diseases · 2025Review
- CD131 contributes to ulcerative colitis pathogenesis by promoting macrophage infiltration.eLife · 2025Article
- Gut microbiota and blood biomarkers in IBD-Related arthritis: insights from mendelian randomization.Scientific reports · 2025Article
- Strategies for targeting cytokines in inflammatory bowel disease.Nature reviews. Immunology · 2024Review
- Effect of vitamin DVeterinarni medicina · 2024Article
- Origin and Function of Monocytes in Inflammatory Bowel Disease.Journal of inflammation research · 2024Review
- Microbial energy metabolism fuels an intestinal macrophage niche in solitary isolated lymphoid tissues through purinergic signaling.Science immunology · 2023Article
- Blood-Based Immune Protein Markers of Disease Progression in Murine Models of Acute and Chronic Inflammatory Bowel Disease.Biomedicines · 2023Article
- Article
- Pattern Recognition Receptor Signaling and Cytokine Networks in Microbial Defenses and Regulation of Intestinal Barriers: Implications for Inflammatory Bowel Disease.Gastroenterology · 2022Review
- Dissecting the role ofFrontiers in immunology · 2022Article
- Inflamed Ulcerative Colitis Regions Associated With MRGPRX2-Mediated Mast Cell Degranulation and Cell Activation Modules, Defining a New Therapeutic Target.Gastroenterology · 2021Article
- Beyond Immunity: Underappreciated Functions of Intestinal Macrophages.Frontiers in immunology · 2021Review
- Use of Single-Cell -Omic Technologies to Study the Gastrointestinal Tract and Diseases, From Single Cell Identities to Patient Features.Gastroenterology · 2020Review
- GM-CSF Calibrates Macrophage Defense and Wound Healing Programs during Intestinal Infection and Inflammation.Cell reports · 2020Article
- NOD2 modulates immune tolerance via the GM-CSF-dependent generation of CD103Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Human Intestinal Mononuclear Phagocytes in Health and Inflammatory Bowel Disease.Frontiers in immunology · 2020Review
- Prioritizing Crohn's disease genes by integrating association signals with gene expression implicates monocyte subsets.Genes and immunity · 2019Article
- Zebrafish modeling of intestinal injury, bacterial exposures and medications defines epithelialDisease models & mechanisms · 2019Article
Corrections and comments
- Commented on by
Authors and funding
60 authors at 20 institutions in 4 countries.
Ling-Shiang ChuangDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
Nicole VillaverdeDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
Ken Y HuiProgram in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut; Section of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.
Arthur MorthaDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
Adeeb RahmanDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
Adam P LevineCentre for Molecular Medicine, Division of Medicine, University College, London, United Kingdom.
Talin HarituniansSection of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.
Sok Meng Evelyn NgSection of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.
Wei ZhangSection of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.
Nai-Yun HsuDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
Jody-Ann FaceyDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
Tramy LuongDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
Heriberto Fernandez-HernandezDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
Dalin LiF. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Manuel RivasDepartment of Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts; Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts; Nuffield Department of Clinical Medicine, Wellcome Trust Centre for Human Genetics Research, University of Oxford, Oxford, United Kingdom.
Elena R SchiffCentre for Molecular Medicine, Division of Medicine, University College, London, United Kingdom.
Alexander GusevDepartment of Epidemiology, Harvard University, Boston, Massachusetts.
L Phillip SchummDepartment of Health Studies, University of Chicago, Chicago, Illinois.
Beatrice M BowenSection of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut; Department of Genetics, Yale University, New Haven, Connecticut.
Yashoda SharmaDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; Section of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.
Kaida NingSection of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut; Department of Molecular and Computational Biology, University of Southern California, Los Angeles, California.
Romain RemarkDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
Sacha GnjaticDivision of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, New York.
Peter LegnaniDivision of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.
James GeorgeDivision of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.
Bruce E SandsDivision of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.
Joanne M StempakZane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Lisa W DattaHarvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Seth LipkaDepartment of Internal Medicine, University of South Florida, Tampa, Florida.
Seymour KatzDepartment of Medicine, New York University School of Medicine, New York, New York.
Adam S CheifetzDivision of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
Nir BarzilaiDepartment of Medicine, Albert Einstein College of Medicine, Bronx, New York.
Nikolas PontikosCentre for Molecular Medicine, Division of Medicine, University College, London, United Kingdom.
Clara AbrahamSection of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.
Marla J DubinskyDivision of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York.
Stephan TarganF. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Kent TaylorInstitute for Translational Genomics and Population Sciences, Division of Genomic Outcomes, Harbor-University of California Los Angeles Medical Center, Torrance, California.
Jerome I RotterInstitute for Translational Genomics and Population Sciences, Division of Genomic Outcomes, Harbor-University of California Los Angeles Medical Center, Torrance, California.
Ellen J ScherlThe Division of Gastroenterology and Hepatology, Sanford I. Weill College of Cornell University-New York Presbyterian Hospital, New York, New York.
Robert J DesnickDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
Maria T AbreuDivision of Gastroenterology, University of Miami, Miller School of Medicine, Miami, Florida.
Hongyu ZhaoDepartment of Biostatistics, Yale University, New Haven, Connecticut.
Gil AtzmonDepartment of Medicine, Albert Einstein College of Medicine, Bronx, New York.
Itsik Pe'erDepartment of Computer Science, Columbia University, New York, New York.
Subra KugathasanDepartment of Pediatrics, Emory University, Atlanta, Georgia.
Hakon HakonarsonCentre for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Division of Human Genetics, University of Pennsylvania, Philadelphia, Pennsylvania.
Jacob L McCauleyJohn P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida; Dr John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, Florida.
Todd LenczFeinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, New York.
Ariel DarvasiDepartment of Genetics, The Hebrew University of Jerusalem, Jerusalem, Israel.
Vincent PlagnolGenetics Institute, Division of Biosciences, University College, London, United Kingdom.
Mark S SilverbergZane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Aleixo M MuiseInflammatory Bowel Disease Centre and Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.
Steven R BrantHarvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Mark J DalyDepartment of Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts; Center for Human Genetic Research, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Department of Genetics, Harvard Medical School, Boston, Massachusetts.
Anthony W SegalCentre for Molecular Medicine, Division of Medicine, University College, London, United Kingdom.
Richard H DuerrDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Miriam MeradDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
Dermot P B McGovernF. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Inga PeterDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
Judy H ChoDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: Judy.cho@mssm.edu.
Icahn School of Medicine at Mount Sinai · USYale University · USUniversity College London · GBCedars-Sinai Medical Center · USAlbert Einstein College of Medicine · USUniversity of Miami · USBeth Israel Deaconess Medical Center · USBroad Institute · USCenter for Human Genetics · USChildren's Hospital of Philadelphia · USColumbia University · USEmory University · USHarvard University · USHebrew University of Jerusalem · ILHospital for Sick Children · CAJohns Hopkins Medicine · USJohns Hopkins University · USLos Angeles Medical Center · USMount Sinai Hospital · CANew York Hospital Queens · US
Funding
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MUCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0MMEDICAL SCIENTIST TRAINING PROGRAMT32GM007205 · NIGMS · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 1985 to 2019
$42.9MUsing polygenic scores to enhance both variant discovery, and understanding of functional consequences of genetic variation in IBD.P01DK046763 · NIDDK · CEDARS-SINAI MEDICAL CENTER · PI TARGAN, STEPHAN R. · 1992 to 2020
$31.1MInflammatory Bowel Disease Genetics Consortium Data Coordinating CenterU01DK062429 · NIDDK · YALE UNIVERSITY · PI CHO, JUDY H. · 2002 to 2016
$16.8MPrecision IBD via genetics and genomics: integrating International and multi-omic datasets, expanding studies in diverse populations, and defining mechanisms of unmet clinical needs in IBDU24DK062429 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Ling-shiang Chuang, Ron Do · 2017 to 2026
$13.9MUtilizing the Phenomics of IBD to Enhance Gene DiscoveryU01DK062413 · NIDDK · CEDARS-SINAI MEDICAL CENTER · PI Dermot Patrick McGovern · 2002 to 2026
$12.2MTranslational Research Enhancement CoreP30DK089502 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI ZACHOS, NICHOLAS CONSTANTINE · 2011 to 2020
$12.0MThe Role of HLA and KIR in Rheumatoid Arthritis and Crohn's DiseaseU01AI067068 · NIAID · STANFORD UNIVERSITY · PI ERLICH, HENRY A, TRACHTENBERG, ELIZABETH A · 2005 to 2014
$10.9MYale University Inflammatory Bowel Disease Genetics Research CenterU01DK062422 · NIDDK · YALE UNIVERSITY · PI Ling-shiang Chuang · 2002 to 2026
$10.8MEinstein's Nathan Shock Center of Excellence in Basic Biology of AgingP30AG038072 · NIA · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI VIJG, JAN · 2010 to 2024
$10.8MIBD Gene Mapping by Clinical and Population SubsetsU01DK062431 · NIDDK · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI Steven R Brant · 2002 to 2026
$10.7MAHRQ HHS R01 HS021747Medical Research Council MR/L000261/1NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1 TR001863NCI NIH HHS R01 CA141743NIAID NIH HHS U01 AI067068NIA NIH HHS P30 AG038072NIA NIH HHS R01 AG046949NIDDK NIH HHS F30 DK098927NIDDK NIH HHS P01 DK046763NIDDK NIH HHS P30 DK089502NIDDK NIH HHS R01 DK092235NIDDK NIH HHS R01 DK099097NIDDK NIH HHS R01 DK106593NIDDK NIH HHS U01 DK062413NIDDK NIH HHS U01 DK062420NIDDK NIH HHS U01 DK062422NIDDK NIH HHS U01 DK062423NIDDK NIH HHS U01 DK062429NIDDK NIH HHS U01 DK062431NIDDK NIH HHS U24 DK062429NIGMS NIH HHS T32 GM007205Wellcome Trust
Abstract
BACKGROUND &
aimsCrohn's disease (CD) has the highest prevalence in Ashkenazi Jewish populations. We sought to identify rare, CD-associated frameshift variants of high functional and statistical effects.
methodsWe performed exome sequencing and array-based genotype analyses of 1477 Ashkenazi Jewish individuals with CD and 2614 Ashkenazi Jewish individuals without CD (controls). To validate our findings, we performed genotype analyses of an additional 1515 CD cases and 7052 controls for frameshift mutations in the colony-stimulating factor 2-receptor β common subunit gene (CSF2RB). Intestinal tissues and blood samples were collected from patients with CD; lamina propria leukocytes were isolated and expression of CSF2RB and granulocyte-macrophage colony-stimulating factor-responsive cells were defined by adenomatous polyposis coli (APC) time-of-flight mass cytometry (CyTOF analysis). Variants of CSF2RB were transfected into HEK293 cells and the expression and functions of gene products were compared.
resultsIn the discovery cohort, we associated CD with a frameshift mutation in CSF2RB (P = 8.52 × 10(-4)); the finding was validated in the replication cohort (combined P = 3.42 × 10(-6)). Incubation of intestinal lamina propria leukocytes with granulocyte-macrophage colony-stimulating factor resulted in high levels of phosphorylation of signal transducer and activator of transcription (STAT5) and lesser increases in phosphorylation of extracellular signal-regulated kinase and AK straining transforming (AKT). Cells co-transfected with full-length and mutant forms of CSF2RB had reduced pSTAT5 after stimulation with granulocyte-macrophage colony-stimulating factor, compared with cells transfected with control CSF2RB, indicating a dominant-negative effect of the mutant gene. Monocytes from patients with CD who were heterozygous for the frameshift mutation (6% of CD cases analyzed) had reduced responses to granulocyte-macrophage colony-stimulating factor and markedly decreased activity of aldehyde dehydrogenase; activity of this enzyme has been associated with immune tolerance.
conclusionsIn a genetic analysis of Ashkenazi Jewish individuals, we associated CD with a frameshift mutation in CSF2RB. Intestinal monocytes from carriers of this mutation had reduced responses to granulocyte-macrophage colony-stimulating factor, providing an additional mechanism for alterations to the innate immune response in individuals with CD.
Indexed as
Frameshift MutationCase-Control StudiesCrohn DiseaseCytokine Receptor Common beta SubunitFemaleGranulocyte-Macrophage Colony-Stimulating FactorHumansIntestinesJewsMaleMonocytesRisk FactorsSignal TransductionCSF2RB protein, humanCytokine Receptor Common beta SubunitGranulocyte-Macrophage Colony-Stimulating FactorEthnic VariationIBDInflammatory Bowel DiseaseRisk Factor
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
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.