Evidence map›Paper›PMID 36680554›Full record

ArticleInflammatory bowel diseases2023

Risk Variants in or Near ZBTB40 AND NFATC1 Increase the Risk of Both IBD and Adverse Bone Health Outcomes Highlighting Common Genetic Underpinnings Across Both Diseases.

Kelly C Cushing, Yanhua Chen, Xiaomeng Du, Vincent Chen, Annapurna Kuppa, Peter Higgins, Elizabeth K Speliotes

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

Article in Inflammatory bowel diseases, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 2 pooled it
1.9field-weighted citation impact, top 14% 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

3 citing papers in PubMed, 2 syntheses or guidelines pooled it, 6 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
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

7 authors at 1 institution in 1 country.

Kelly C CushingDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0003-3914-9673
Yanhua ChenDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Xiaomeng DuDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Vincent ChenDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Annapurna KuppaDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Peter HigginsDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Elizabeth K SpeliotesDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
University of Michigan · US

Funding

Training Program in Gastrointestinal EpidemiologyT32DK062708 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Peter D.R. Higgins, Elliot Tapper · 2003 to 2026
$3.9M
Identification and functional impact of NAFLD associated genetic variantsR01DK106621 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SPELIOTES, ELIZABETH K · 2015 to 2019
$3.3M
Measuring Molecular and Mechanical Outcomes of Endoscopic Dilation of Fibrotic StricturesR01DK125687 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Peter D.R. Higgins, Guan Xu · 2020 to 2026
$3.3M
Integrative Polygenic Genetic Studies of Non-alcoholic Fatty Liver DiseaseR01DK131787 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SPELIOTES, ELIZABETH K · 2022 to 2025
$2.7M
Identification and Characterization of Loci Associated with Non-alcoholic Fatty Liver DiseaseR01DK128871 · NIDDK · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ALLRED, NICHOLETTE D., SPELIOTES, ELIZABETH K · 2021 to 2024
$2.6M
Inhibiting Bcl-2-regulated intestinal fibrosis in models of Crohn’s DiseaseR01DK118154 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HIGGINS, PETER D.R. · 2018 to 2022
$2.3M
Mechanism, Modification, and Intervention in a Pre-Clinical Model of GalactosemiaR01DK107900 · NIDDK · EMORY UNIVERSITY · PI FRIDOVICH-KEIL, JUDITH L. · 2016 to 2019
$1.8M
Predictive models for incident cirrhosis in non-alcoholic fatty liver disease using genetic and electronic medical record-based risk factorsK08DK132312 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Vincent Lingzhi Chen · 2022 to 2026
$834k
NIDDK NIH HHS K08 DK132312NIDDK NIH HHS R01 DK106621NIDDK NIH HHS R01 DK107900NIDDK NIH HHS R01 DK118154NIDDK NIH HHS R01 DK125687NIDDK NIH HHS R01 DK131787
6 · The paper itself

Abstract

backgroundInflammatory bowel disease (IBD) is associated with an increased risk of osteoporosis and bone fracture. The aims of this study were to (1) confirm the association between IBD and low bone density and (2) test for shared risk variants across diseases.

methodsThe study cohort included patients from the Michigan Genomics Initiative. Student's t tests (continuous) and chi-square tests (categorical) were used for univariate analyses. Multivariable logistic regression was performed to test the effect of IBD on osteoporosis or osteopenia. Publicly available genome-wide association summary statistics were used to identify variants that alter the risk of IBD and bone density, and Mendelian randomization (MR) was used to identify causal effects of genetically predicted IBD on bone density.

resultsThere were 51 405 individuals in the Michigan Genomics Initiative cohort including 10 378 (20.2%) cases of osteoporosis or osteopenia and 1404 (2.7%) cases of IBD. Patients with osteoporosis or osteopenia were more likely to be older (64 years of age vs 56 years of age; P < .001), female (67% vs 49%; P < .001), and have a lower body mass index (29 kg/m2 vs 30 kg/m2; P < .001). IBD patients with (odds ratio, 4.60; 95% confidence interval, 3.93-5.37) and without (odds ratio, 1.77; 95% confidence interval, 1.42-2.21) steroid use had a significantly higher risk of osteoporosis or osteopenia. Twenty-one IBD variants associated with reduced bone mineral density at P ≤ .05 and 3 IBD risk variants associated with reduced bone mineral density at P ≤ 5 × 10-8. Of the 3 genome-wide significant variants, 2 increased risk of IBD (rs12568930-T: MIR4418;ZBTB40; rs7236492-C: NFATC1). MR did not reveal a causal effect of genetically predicted IBD on bone density (MR Egger, P = .30; inverse variance weighted, P = .63).

conclusionsPatients with IBD are at increased risk for low bone density, independent of steroid use. Variants in or near ZBTB40 and NFATC1 are associated with an increased risk of IBD and low bone density.

Indexed as

Bone Diseases, MetabolicInflammatory Bowel DiseasesOsteoporosisBone DensityFemaleGenome-Wide Association StudyHumansMiddle AgedNFATC Transcription FactorsOutcome Assessment, Health CareSteroidsNFATC1 protein, humanNFATC Transcription FactorsSteroidsgeneticsinflammatory bowel diseaseosteoporosis

Identifiers

PMID36680554
PMCPMC10465078
OpenAlexW4317663957

What Socratic holds

Textmetadata
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 Socratic graph.