Evidence map›Paper›PMID 38490347›Full record

ArticleGastroenterology2024

Comprehensive Association Analyses of Extraintestinal Manifestations in Inflammatory Bowel Disease.

Michelle Khrom, Millie Long, Shishir Dube, Lori Robbins, Gregory J Botwin, Shaohong Yang, Emebet Mengesha, Dalin Li, Takeo Naito, Nirupama N Bonthala and 25 more

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

Article in Gastroenterology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 2 pooled it
20.9field-weighted citation impact, top 1% 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

33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 38 citations in OpenAlex.

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  13. Journal of clinical medicine · 2026
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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

35 authors at 15 institutions in 2 countries.

Michelle KhromF. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Millie LongCenter for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, North Carolina.
Shishir DubeF. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Lori RobbinsPalmetto Digestive Health Specialists, Charleston, South Carolina.
Gregory J BotwinF. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Shaohong YangF. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Emebet MengeshaF. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Dalin LiF. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Takeo NaitoF. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Nirupama N BonthalaF. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Christina HaInflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California.
Gil MelmedInflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California.
Shervin RabizadehDepartment of Pediatrics, Pediatric Inflammatory Bowel Disease Program, Cedars-Sinai Medical Center, Los Angeles, California.
Gaurav SyalInflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California.
Eric VasiliauskasInflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California.
David ZiringInflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California.
Steven R BrantDivision of Gastroenterology and Hepatology, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey.
Judy ChoIcahn School of Medicine at Mount Sinai, Dr Henry D. Janowitz Division of Gastroenterology, New York, New York.
Richard H DuerrDivision of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
John RiouxDepartment of Medicine, Université de Montréal and Research Center, Montreal Heart Institute, Montréal, Québec, Canada.
Phil SchummDepartment of Public Health Sciences, University of Chicago, Chicago, Illinois.
Mark SilverbergUniversity of Toronto, Samuel Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Ashwin N AnanthakrishnanGastroenterology, Massachusetts General Hospital, Boston, Massachusetts.
William A FaubionMayo Clinic, Rochester, Minnesota.
Bana JabriUniversity of Chicago, Pritzker School of Medicine, Chicago, Illinois.
Sergio A LiraImmunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Rodney D NewberryDepartment of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri.
Robert S SandlerCenter for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, North Carolina.
Ramnik J XavierBroad Institute of MIT and Harvard, Cambridge, Massachusetts.
Subra KugathasanChildren's Healthcare of Atlanta Combined Center for Pediatric Inflammatory Bowel Disease, Atlanta, Georgia; Emory School of Medicine, Atlanta, Georgia.
David HerculesEmory School of Medicine, Atlanta, Georgia.
Stephan R TarganF. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California.
R Balfour SartorCenter for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, North Carolina.
Talin HarituniansF. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Dermot P B McGovernF. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address: Dermot.McGovern@cshs.org.
Cedars-Sinai Medical Center · USUniversity of North Carolina at Chapel Hill · USEmory University · USIcahn School of Medicine at Mount Sinai · USBroad Institute · USChicago Department of Public Health · USFlorida Digestive Health Specialists · USMassachusetts General Hospital · USMayo Clinic · USMontreal Heart Institute · CAMount Sinai Hospital · CARutgers, The State University of New Jersey · USUniversity of Chicago · USUniversity of Pittsburgh · USWashington University in St. Louis · US

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Ramnik J Xavier · 1991 to 2026
$35.3M
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 MCGOVERN, DERMOT PATRICK · 1992 to 2020
$31.1M
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
IBD Gene Mapping by Clinical and Population SubsetsU01DK062431 · NIDDK · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI Steven R Brant · 2002 to 2026
$10.7M
Impact of Genetic Variability on Cellular Pathways and Host-Microbiome InteractioU01DK062423 · NIDDK · SINAI HEALTH SYSTEM · PI MARK S. SILVERBERG · 2002 to 2026
$7.5M
Mechanisms associated with flares and remission in colitisR01DK110352 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI LIRA, SERGIO A. · 2017 to 2025
$5.1M
Mechanisms associated with diet-induced colitisR01DK121009 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI LIRA, SERGIO A. · 2020 to 2023
$2.4M
NIDDK NIH HHS P01 DK046763NIDDK NIH HHS P30 DK043351NIDDK NIH HHS R01 DK110352NIDDK NIH HHS R01 DK121009NIDDK NIH HHS U01 DK062413NIDDK NIH HHS U01 DK062422NIDDK NIH HHS U01 DK062423NIDDK NIH HHS U01 DK062431NIDDK NIH HHS U24 DK062429
6 · The paper itself

Abstract

BACKGROUND &

aimsPatients with inflammatory bowel disease (IBD) frequently develop extraintestinal manifestations (EIMs) that contribute substantially to morbidity. We assembled the largest multicohort data set to date to investigate the clinical, serologic, and genetic factors associated with EIM complications in IBD.

methodsData were available in 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs (eg, ankylosing spondylitis [ankylosing spondylitis and sacroiliitis], primary sclerosing cholangitis [PSC], peripheral arthritis, and skin and ocular manifestations) across 4 cohorts (Cedars-Sinai Medical Center, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn's Disease cohort). Clinical and serologic parameters were analyzed by means of univariable and multivariable regression analyses using a mixed-effects model. Within-case logistic regression was performed to assess genetic associations.

resultsMost EIMs occurred more commonly in female subjects (overall EIM: P = 9.0E-05, odds ratio [OR], 1.2; 95% CI, 1.1-1.4), with CD (especially colonic disease location; P = 9.8E-09, OR, 1.7; 95% CI, 1.4-2.0), and in subjects who required surgery (both CD and UC; P = 3.6E-19, OR, 1.7; 95% CI, 1.5-1.9). Smoking increased risk of EIMs except for PSC, where there was a "protective" effect. Multiple serologic associations were observed, including with PSC (anti-nuclear cytoplasmic antibody; IgG and IgA, anti-Saccharomyces cerevisiae antibodies; and anti-flagellin) and any EIM (anti-nuclear cytoplasmic antibody; IgG and IgA, anti-Saccharomyces cerevisiae antibodies; and anti-Pseudomonas fluorescens-associated sequence). We identified genome-wide significant associations within major histocompatibility complex (ankylosing spondylitis and sacroiliitis, P = 1.4E-15; OR, 2.5; 95% CI, 2.0-3.1; PSC, P = 2.7E-10; OR, 2.8; 95% CI, 2.0-3.8; ocular, P = 2E-08, OR, 3.6; 95% CI, 2.3-5.6; and overall EIM, P = 8.4E-09; OR, 2.2; 95% CI, 1.7-2.9) and CPEB4 (skin, P = 2.7E-08; OR, 1.5; 95% CI, 1.3-1.8). Genetic associations implicated tumor necrosis factor, JAK-STAT, and IL6 as potential targets for EIMs. Contrary to previous reports, only 2% of our subjects had multiple EIMs and most co-occurrences were negatively correlated.

conclusionsWe have identified demographic, clinical, and genetic associations with EIMs that revealed underlying mechanisms and implicated novel and existing drug targets-important steps toward a more personalized approach to IBD management.

Indexed as

Cholangitis, SclerosingColitis, UlcerativeCrohn DiseaseAdolescentAdultAgedChildEye DiseasesFemaleGenetic Predisposition to DiseaseHumansInflammatory Bowel DiseasesLogistic ModelsMaleMiddle AgedPhenotypeExtraintestinal ManifestationsGeneticsInflammatory Bowel DiseaseSerology

Identifiers

PMID38490347
PMCPMC11193636
OpenAlexW4392750793

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.