Evidence map›Paper›PMID 31891614›Full record

SynthesisPloS one2019

Identification of loci of functional relevance to Barrett's esophagus and esophageal adenocarcinoma: Cross-referencing of expression quantitative trait loci data from disease-relevant tissues with genetic association data.

Julia Schröder, Vitalia Schüller, Andrea May, Christian Gerges, Mario Anders, Jessica Becker, Timo Hess, Nicole Kreuser, René Thieme, Kerstin U Ludwig and 31 more

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 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

7 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Article
  6. Article
  7. Mechanisms and pathophysiology of Barrett oesophagus.Nature reviews. Gastroenterology & hepatology · 2022
    Review
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.

Julia SchröderInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.ORCID 0000-0002-5278-7904
Vitalia SchüllerInstitute for Medical Biometry, Informatics, and Epidemiology, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
Andrea MayDepartment of Medicine II, Sana Klinikum, Offenbach, Germany.
Christian GergesDepartment of Internal Medicine II, Evangelisches Krankenhaus, Düsseldorf, Germany.
Mario AndersDepartment of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Jessica BeckerInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
Timo HessInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
Nicole KreuserDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.
René ThiemeDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.ORCID 0000-0002-0537-3979
Kerstin U LudwigInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
Tania NoderDepartment of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Marino VeneritoDepartment of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany.ORCID 0000-0001-8581-0974
Lothar VeitsInstitute of Pathology, Klinikum Bayreuth, Bayreuth, Germany.
Thomas SchmidtDepartment of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.ORCID 0000-0002-7166-3675
Claudia FuchsDepartment of General, Visceral, and Cancer Surgery, University of Cologne, Cologne, Germany.
Jakob R IzbickiDepartment of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.
Arnulf H HölscherDepartment of General, Visceral, and Cancer Surgery, University of Cologne, Cologne, Germany.
Dani DakkakDepartment of Internal Medicine and Gastroenterology, Elisabeth Hospital, Essen, Germany.
Boris Jansen-WinkelnDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.ORCID 0000-0002-3996-9391
Yusef MoullaDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.
Orestis LyrosDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.
Stefan NiebischDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.
Matthias MehdornDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.
Hauke LangDepartment of General, Visceral, and Transplant Surgery, University Medical Center, University of Mainz, Mainz, Germany.
Dietmar LorenzDepartment of General, Visceral, and Thoracic Surgery, Klinikum Darmstadt, Darmstadt, Germany.
Brigitte SchumacherDepartment of Internal Medicine and Gastroenterology, Elisabeth Hospital, Essen, Germany.
Rupert MayershoferGastroenterologie am Burgweiher, Bonn, Germany.
Yogesh VashistDepartment of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.
Katja OttDepartment of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
Michael ViethInstitute of Pathology, Klinikum Bayreuth, Bayreuth, Germany.
Josef WeismüllerGastroenterologische Gemeinschaftspraxis, Koblenz, Germany.
Elisabeth MangoldInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
Markus M NöthenInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.ORCID 0000-0002-8770-2464
Susanne MoebusCentre of Urban Epidemiology, Institute of Medical Informatics, Biometry, and Epidemiology, University of Essen, Essen, Germany.
Michael KnappInstitute for Medical Biometry, Informatics, and Epidemiology, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
Horst NeuhausDepartment of Internal Medicine II, Evangelisches Krankenhaus, Düsseldorf, Germany.
Thomas RöschDepartment of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Christian EllDepartment of Medicine II, Sana Klinikum, Offenbach, Germany.
Ines GockelDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.
Johannes SchumacherCenter for Human Genetics, University Hospital Marburg, Marburg, Germany.
Anne C BöhmerInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Esophageal adenocarcinoma (EA) and its precancerous condition Barrett's esophagus (BE) are multifactorial diseases with rising prevalence rates in Western populations. A recent meta-analysis of genome-wide association studies (GWAS) data identified 14 BE/EA risk loci located in non-coding genomic regions. Knowledge about the impact of non-coding variation on disease pathology is incomplete and needs further investigation. The aim of the present study was (i) to identify candidate genes of functional relevance to BE/EA at known risk loci and (ii) to find novel risk loci among the suggestively associated variants through the integration of expression quantitative trait loci (eQTL) and genetic association data. eQTL data from two BE/EA-relevant tissues (esophageal mucosa and gastroesophageal junction) generated within the context of the GTEx project were cross-referenced with the GWAS meta-analysis data. Variants representing an eQTL in at least one of the two tissues were categorized into genome-wide significant loci (P < 5×10-8) and novel candidate loci (5×10-8 ≤ P ≤ 5×10-5). To follow up these novel candidate loci, a genetic association study was performed in a replication cohort comprising 1,993 cases and 967 controls followed by a combined analysis with the GWAS meta-analysis data. The cross-referencing of eQTL and genetic data yielded 2,180 variants that represented 25 loci. Among the previously reported genome-wide significant loci, 22 eQTLs were identified in esophageal mucosa and/or gastroesophageal junction tissue. The regulated genes, most of which have not been linked to BE/EA etiology so far, included C2orf43/LDAH, ZFP57, and SLC9A3. Among the novel candidate loci, replication was achieved for two variants (rs7754014, Pcombined = 3.16×10-7 and rs1540, Pcombined = 4.16×10-6) which represent eQTLs for CFDP1 and SLC22A3, respectively. In summary, the present approach identified candidate genes whose expression was regulated by risk variants in disease-relevant tissues. These findings may facilitate the elucidation of BE/EA pathophysiology.

Indexed as

Gene Expression Regulation, NeoplasticQuantitative Trait LociAdenocarcinomaBarrett EsophagusEsophageal MucosaEsophageal NeoplasmsGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPolymorphism, Single NucleotideProteinsRepressor ProteinsSodium-Hydrogen Exchanger 3LDAH protein, humanProteinsRepressor ProteinsSLC9A3 protein, humanSodium-Hydrogen Exchanger 3ZFP57 protein, human

Identifiers

PMID31891614
PMCPMC6938334

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