Evidence map›Paper›PMID 27037036›Full record

ArticleBMC medical genetics2016

Genome-wide rare copy number variation screening in ulcerative colitis identifies potential susceptibility loci.

Hamid Reza Saadati, Michael Wittig, Ingo Helbig, Robert Häsler, Carl A Anderson, Christopher G Mathew, Limas Kupcinskas, Miles Parkes, Tom Hemming Karlsen, Philip Rosenstiel and 2 more

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

Article in BMC medical genetics, 2016. 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
1.8field-weighted citation impact, top 13% 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

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Article
  6. Review
  7. 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

12 authors at 7 institutions in 4 countries.

Hamid Reza SaadatiInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Schittenhelmstr. 12, 24105, Kiel, Germany.
Michael WittigInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Schittenhelmstr. 12, 24105, Kiel, Germany.
Ingo HelbigDepartment of Neuropediatrics, University Clinic Schleswig-Holstein, Campus Kiel, Arnold-Heller-Strasse 3, Building 9, 24105, Kiel, Germany.
Robert HäslerInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Schittenhelmstr. 12, 24105, Kiel, Germany.
Carl A AndersonWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
Christopher G MathewDepartment of Medical and Molecular Genetics, King's College London School of Medicine, London, UK.
Limas KupcinskasInstitute for Digestive Research, Lithuanian University of Health Sciences, Mickeviciaus 9, Kaunas, LT, 44307, Lithuania.
Miles ParkesInflammatory Bowel Disease Research Group, Addenbrooke's Hospital, University of Cambridge, Cambridge, CB2 2QQ, UK.
Tom Hemming KarlsenNorwegian PSC Research Center, Clinic for Specialized Medicine and Surgery, Oslo University Hospital, Rikshospitalet, 0027, Oslo, Norway.
Philip RosenstielInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Schittenhelmstr. 12, 24105, Kiel, Germany.
Stefan SchreiberInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Schittenhelmstr. 12, 24105, Kiel, Germany.
Andre FrankeInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Schittenhelmstr. 12, 24105, Kiel, Germany. a.franke@mucosa.de.
Kiel University · DEKing's College London · GBLithuanian University of Health Sciences · LTOslo University Hospital · NOUniversity of Cambridge · GBUniversity of Lübeck · DEWellcome Sanger Institute · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundUlcerative colitis (UC), a complex polygenic disorder, is one of the main subphenotypes of inflammatory bowel disease. A comprehensive dissection of the genetic etiology of UC needs to assess the contribution of rare genetic variants including copy number variations (CNVs) to disease risk. In this study, we performed a multi-step genome-wide case-control analysis to interrogate the presence of disease-relevant rare copy number variants.

methodsOne thousand one hundred twenty-one German UC patients and 1770 healthy controls were initially screened for rare deletions and duplications employing SNP-array data. Quantitative PCR and high density custom array-CGH were used for validation of identified CNVs and fine mapping. Two main follow-up panels consisted of an independent cohort of 451 cases and 1274 controls, in which CNVs were assayed through quantitative PCR, and a British cohort of 2396 cases versus 4886 controls with CNV genotypes based on array data. Additional sample sets were assessed for targeted and in silico replication.

resultsTwenty-four rare copy number variants (14 deletions and 10 duplications), overrepresented in UC patients were identified in the initial screening panel. Follow-up of these CNV regions in four independent case-control series as well as an additional public in silico control group (totaling 4439 UC patients and 15,961 healthy controls) revealed three copy number variants enriched in UC patients; a 15.8 kb deletion upstream of ABCC4 and CLDN10 at13q32.1 (0.43% cases, 0.11% controls), a 119 kb duplication at 7p22.1, overlapping RNF216, ZNF815, OCM and CCZ1 (0.13% cases, 0.01% controls) and a 134 kb large duplication upstream of the KCNK9 gene at 8q24.3 (0.22% carriers among cases, 0.03% carriers among controls). The trend of association with UC was present after the P-values were corrected for combining data from different subpopulations. Break-point mapping of the deleted region suggested non-allelic homologous recombination as the mechanism underlying its formation.

conclusionOur study presents a pragmatic approach for effective rare CNV screening of SNP-array data sets and implicates the potential contribution of rare structural variants in the pathogenesis of UC.

Indexed as

DNA Copy Number VariationsAdolescentAdultAgedAged, 80 and overCase-Control StudiesColitis, UlcerativeComparative Genomic HybridizationFemaleGene DeletionGene DuplicationGenetic LociGenome-Wide Association StudyHumansMaleMiddle AgedCase-control associationCopy number variationRare variantsSNP arrayUlcerative colitis

Identifiers

PMID27037036
PMCPMC4818401
OpenAlexW2331530084

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.