Evidence map›Paper›PMID 33590606›Full record

ArticleLiver international : official journal of the International Association for the Study of the Liver2021

Exome sequencing in patient-parent trios suggests new candidate genes for early-onset primary sclerosing cholangitis.

Sjoukje-Marije Haisma, Rinse K Weersma, Maria E Joosse, Barbara A E de Koning, Tim de Meij, Bart G P Koot, Victorien Wolters, Obbe Norbruis, Mark J Daly, Christine Stevens and 10 more

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

Article in Liver international : official journal of the International Association for the Study of the Liver, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.8field-weighted citation impact, top 28% 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

5 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Exome sequencing in patient-parent trios suggests new candidate genes for early-onset primary sclerosing cholangitis.Liver international : official journal of the International Association for the Study of the Liver · 2021
    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

20 authors at 10 institutions in 3 countries.

Sjoukje-Marije HaismaDepartment of Paediatric Gastroenterology Hepatology and Nutrition, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.ORCID 0000-0003-4814-7776
Rinse K WeersmaDepartment of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Maria E JoosseDepartment of Paediatric Gastroenterology, Erasmus University Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands.ORCID 0000-0001-7420-7125
Barbara A E de KoningDepartment of Paediatric Gastroenterology, Erasmus University Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands.
Tim de MeijDepartment of Pediatric Gastroenterology, VU University Medical Center, Amsterdam, The Netherlands.
Bart G P KootPediatric Gastroenterology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Victorien WoltersDepartment of Pediatric Gastroenterology, University Medical Center Utrecht - Wilhelmina Children's Hospital, Utrecht, The Netherlands.
Obbe NorbruisDepartment of Pediatrics, Isala Hospital, Zwolle, The Netherlands.
Mark J DalyBroad Institute of Harvard and Massachusetts Institute of Technology, Boston, MA, USA.
Christine StevensBroad Institute of Harvard and Massachusetts Institute of Technology, Boston, MA, USA.
Ramnik J XavierMassachusetts General Hospital, Gastroenterology, Boston, MA, USA.
Jukka KoskelaMassachusetts General Hospital, Gastroenterology, Boston, MA, USA.ORCID 0000-0002-0154-7222
Manuel A RivasStanford University, Stanford, CA, United States.
Marijn C VisschedijkDepartment of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Henkjan J VerkadeDepartment of Paediatric Gastroenterology Hepatology and Nutrition, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Ruggero BarbieriDepartment of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Dianne B H JansenDepartment of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Eleonora A M FestenDepartment of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Patrick F van RheenenDepartment of Paediatric Gastroenterology Hepatology and Nutrition, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Cleo C van DiemenDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
University Medical Center Groningen · NLBroad Institute · USErasmus MC · NLAmsterdam UMC Location Vrije Universiteit Amsterdam · NLEmma Kinderziekenhuis · NLIsala · NLMassachusetts General Hospital · USStanford University · USUniversity Medical Center Utrecht · NLUniversity of Helsinki · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

aimsPrimary sclerosing cholangitis (PSC) is a rare bile duct disease strongly associated with inflammatory bowel disease (IBD). Whole-exome sequencing (WES) has contributed to understanding the molecular basis of very early-onset IBD, but rare protein-altering genetic variants have not been identified for early-onset PSC. We performed WES in patients diagnosed with PSC ≤ 12 years to investigate the contribution of rare genetic variants to early-onset PSC.

methodsIn this multicentre study, WES was performed on 87 DNA samples from 29 patient-parent trios with early-onset PSC. We selected rare (minor allele frequency < 2%) coding and splice-site variants that matched recessive (homozygous and compound heterozygous variants) and dominant (de novo) inheritance in the index patients. Variant pathogenicity was predicted by an in-house developed algorithm (GAVIN), and PSC-relevant variants were selected using gene expression data and gene function.

resultsIn 22 of 29 trios we identified at least 1 possibly pathogenic variant. We prioritized 36 genes, harbouring a total of 54 variants with predicted pathogenic effects. In 18 genes, we identified 36 compound heterozygous variants, whereas in the other 18 genes we identified 18 de novo variants. Twelve of 36 candidate risk genes are known to play a role in transmembrane transport, adaptive and innate immunity, and epithelial barrier function.

conclusionsThe 36 candidate genes for early-onset PSC need further verification in other patient cohorts and evaluation of gene function before a causal role can be attributed to its variants.

Indexed as

Cholangitis, SclerosingInflammatory Bowel DiseasesExomeExome SequencingHumansParentsgeneticinflammatory bowel diseasesclerosing cholangitis

Identifiers

PMID33590606
PMCPMC8252477
OpenAlexW3131148204

What OpenQuestion holds

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Registered trials

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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.