Evidence map›Paper›PMID 29091079›Full record

ArticleMucosal immunology2018

NOX1 loss-of-function genetic variants in patients with inflammatory bowel disease.

T Schwerd, R V Bryant, S Pandey, M Capitani, L Meran, J-B Cazier, J Jung, K Mondal, M Parkes, C G Mathew and 31 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Mucosal immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
4.2field-weighted citation impact, top 5% of its field
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

54 citing papers in PubMed, 89 citations in OpenAlex.

  1. Trial
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  12. The Impact of Pentraxin 3 on Crohn's Disease Phenotype.International journal of molecular sciences · 2024
    Article
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  14. Review
  15. Article
  16. Article
  17. Integrated genomic network analysis revealed potential of a druggable target for hemorrhoid treatment.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023
    Article
  18. Review
  19. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

41 authors at 20 institutions in 6 countries.

T SchwerdTranslational Gastroenterology Unit, University of Oxford, Oxford, UK.
R V BryantTranslational Gastroenterology Unit, University of Oxford, Oxford, UK.
S PandeyTranslational Gastroenterology Unit, University of Oxford, Oxford, UK.
M CapitaniTranslational Gastroenterology Unit, University of Oxford, Oxford, UK.
L MeranThe Francis Crick Institute, London, UK.
J-B CazierThe Wellcome Trust Centre for Human Genetics, Oxford, UK.
J JungTranslational Gastroenterology Unit, University of Oxford, Oxford, UK.
K MondalDivision of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory University, Atlanta, Georgia, USA.
M ParkesInflammatory Bowel Disease Research Group, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
C G MathewDepartment of Medical and Molecular Genetics, King's College London School of Medicine, Guy's Hospital London, London, UK.
K FiedlerSickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
D J McCarthyThe Wellcome Trust Centre for Human Genetics, Oxford, UK.
WGS500 Consortium
Oxford IBD cohort study investigators
COLORS in IBD group investigators
UK IBD Genetics Consortium
P B SullivanDepartment of Paediatrics, University of Oxford, Oxford, UK.
A RodriguesDepartment of Paediatrics, University of Oxford, Oxford, UK.
S P L TravisTranslational Gastroenterology Unit, University of Oxford, Oxford, UK.
C MooreNIHR Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
J SambrookINTERVAL Coordinating Centre, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
W H OuwehandNIHR Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
D J RobertsNIHR Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
J DaneshNIHR Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
INTERVAL Study
R K RussellDepartment of Paediatric Gastroenterology, The Royal Hospital for Children, Glasgow, UK.
D C WilsonRoyal Hospital for Sick Children, Edinburgh, UK.
J R KelsenDivision of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
R CornallCentre for Cellular and Molecular Physiology, University of Oxford, Oxford, UK.
L A DensonDivision of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
S KugathasanDivision of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory University, Atlanta, Georgia, USA.
U G KnausConway Institute, School of Medicine, University College Dublin, Dublin, Ireland.
E G SerraWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
C A AndersonWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
R H DuerrDivision of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
D Pb McGovernF. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
J ChoIcahn School of Medicine, Mount Sinai Hospital, New York, New York, USA.
F PowrieKennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
V Sw LiThe Francis Crick Institute, London, UK.
A M MuiseSickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
H H UhligTranslational Gastroenterology Unit, University of Oxford, Oxford, UK.
University of Oxford · GBUniversity of Cambridge · GBEmory University · USThe Francis Crick Institute · GBWellcome Sanger Institute · GBAddenbrooke's Hospital · GBCedars-Sinai Medical Center · USCentre for Human Genetics · GBChildren's Health Ireland at Crumlin · IEChildren's Hospital of Philadelphia · USCincinnati Children's Hospital Medical Center · USEuropean Bioinformatics Institute · GBGenomics (United Kingdom) · GBKing's College London · GBMount Sinai Hospital · USNHS Blood and Transplant · GBRoyal Hospital for Children · GBSickKids Foundation · CAUniversity of Adelaide · AUUniversity of Edinburgh · GB

Funding

Using 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
$31.1M
Stem Cell/Organoid and Genome Editing CoreP30DK078392 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI Alexander Miethke · 2007 to 2026
$24.4M
Precision 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
$13.9M
Utilizing the Phenomics of IBD to Enhance Gene DiscoveryU01DK062413 · NIDDK · CEDARS-SINAI MEDICAL CENTER · PI Dermot Patrick McGovern · 2002 to 2026
$12.2M
Yale University Inflammatory Bowel Disease Genetics Research CenterU01DK062422 · NIDDK · YALE UNIVERSITY · PI Ling-shiang Chuang · 2002 to 2026
$10.8M
NIDDK IBD Genetics Consortium Genetic Research CenterU01DK062420 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DUERR, RICHARD H · 2002 to 2021
$7.8M
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
Very Early-onset inflammatory bowel diseaseK23DK100461 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI KELSEN, JUDITH RACHEL · 2014 to 2018
$893k
Replication of Association Signals Identified in Ulcerative Colitis GWASR01CA141743 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DUERR, RICHARD H · 2009 to 2010
$600k
British Heart Foundation RG/13/13/30194British Heart Foundation SP/09/002Chief Scientist Office ETM/137Department of Health NIHR-RP-R3-12-026Medical Research Council G0600329Medical Research Council G0800270Medical Research Council G0800675Medical Research Council G0800759Medical Research Council G0900747 91070Medical Research Council MC_UP_1202/7Medical Research Council MC_UP_A390_1107Medical Research Council MC_UU_00008/6Medical Research Council MC_UU_00008/7Medical Research Council MC_UU_12010/6Medical Research Council MC_UU_12010/7Medical Research Council MR/L003120/1MRF_ C0482NCI NIH HHS R01 CA141743NIDDK NIH HHS K23 DK100461NIDDK NIH HHS P01 DK046763NIDDK NIH HHS P30 DK078392NIDDK NIH HHS R01 DK098231NIDDK NIH HHS U01 DK062413NIDDK NIH HHS U01 DK062420NIDDK NIH HHS U01 DK062422NIDDK NIH HHS U24 DK062429Wellcome Trust 090532/Z/09/ZWellcome Trust 109965/Z/15/Z
6 · The paper itself

Abstract

Genetic defects that affect intestinal epithelial barrier function can present with very early-onset inflammatory bowel disease (VEOIBD). Using whole-genome sequencing, a novel hemizygous defect in NOX1 encoding NAPDH oxidase 1 was identified in a patient with ulcerative colitis-like VEOIBD. Exome screening of 1,878 pediatric patients identified further seven male inflammatory bowel disease (IBD) patients with rare NOX1 mutations. Loss-of-function was validated in p.N122H and p.T497A, and to a lesser degree in p.Y470H, p.R287Q, p.I67M, p.Q293R as well as the previously described p.P330S, and the common NOX1 SNP p.D360N (rs34688635) variant. The missense mutation p.N122H abrogated reactive oxygen species (ROS) production in cell lines, ex vivo colonic explants, and patient-derived colonic organoid cultures. Within colonic crypts, NOX1 constitutively generates a high level of ROS in the crypt lumen. Analysis of 9,513 controls and 11,140 IBD patients of non-Jewish European ancestry did not reveal an association between p.D360N and IBD. Our data suggest that loss-of-function variants in NOX1 do not cause a Mendelian disorder of high penetrance but are a context-specific modifier. Our results implicate that variants in NOX1 change brush border ROS within colonic crypts at the interface between the epithelium and luminal microbes.

Indexed as

GenotypeAnimalsChildChild, PreschoolColonGenes, ModifierGenetic Association StudiesGenetic Predisposition to DiseaseGenomeHigh-Throughput Nucleotide SequencingHost-Pathogen InteractionsHumansInflammatory Bowel DiseasesMaleMiceMice, Inbred C57BLNADPH Oxidase 1NOX1 protein, humanReactive Oxygen Species

Identifiers

PMID29091079
PMCPMC5924597
OpenAlexW2765628679

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.