Evidence map›Paper›PMID 34033851›Full record

SynthesisJournal of hepatology2021

An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs.

Heather J Cordell, James J Fryett, Kazuko Ueno, Rebecca Darlay, Yoshihiro Aiba, Yuki Hitomi, Minae Kawashima, Nao Nishida, Seik-Soon Khor, Olivier Gervais and 40 more

Erratum issuedOpen access · hybridAbstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in Journal of hepatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 105 papers, 14 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
105citing papers in PubMed, 14 pooled it
15.1field-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

105 citing papers in PubMed, 14 syntheses or guidelines pooled it, 178 citations in OpenAlex.

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  15. Review
  16. rs57494551 increases CXCR5 expression and IgMJournal of gastroenterology · 2026
    Article
  17. Article
  18. Article
  19. Genetic testing in liver diseases: Clinical applications.JHEP reports : innovation in hepatology · 2026
    Review
  20. Article

45 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

50 authors at 16 institutions in 6 countries.

Heather J CordellPopulation Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
James J FryettPopulation Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
Kazuko UenoGenome Medical Science Project, National Center for Global Health and Medicine (NCGM), Tokyo, Japan.
Rebecca DarlayPopulation Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
Yoshihiro AibaClinical Research Center, National Hospital Organization, Nagasaki Medical Center, Omura, Japan.
Yuki HitomiDepartment of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Minae KawashimaDepartment of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Nao NishidaDepartment of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Seik-Soon KhorGenome Medical Science Project, National Center for Global Health and Medicine (NCGM), Tokyo, Japan.
Olivier GervaisHuman Biosciences Unit for the Top Global Course Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan; Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Yosuke KawaiGenome Medical Science Project, National Center for Global Health and Medicine (NCGM), Tokyo, Japan.
Masao NagasakiHuman Biosciences Unit for the Top Global Course Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan; Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Katsushi TokunagaGenome Medical Science Project, National Center for Global Health and Medicine (NCGM), Tokyo, Japan.
Ruqi TangDivision of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai Institute of Digestive Disease, Shanghai, China.
Yongyong ShiBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Collaborative Innovation Center for Brain Science, Shanghai Jiao Tong University, Shanghai, China; Affiliated Hospital of Qingdao University and Biomedical Sciences Institute of Qingdao University (Qingdao Branch of SJTU Bio-X Institutes), Qingdao University, Qingdao, China.
Zhiqiang LiBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Collaborative Innovation Center for Brain Science, Shanghai Jiao Tong University, Shanghai, China; Affiliated Hospital of Qingdao University and Biomedical Sciences Institute of Qingdao University (Qingdao Branch of SJTU Bio-X Institutes), Qingdao University, Qingdao, China.
Brian D JuranDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, United States.
Elizabeth J AtkinsonDivision of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, United States.
Alessio GerussiDivision of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy.
Marco CarboneDivision of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy.
Rosanna AsseltaDepartment of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy.
Angela CheungDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, United States.
Mariza de AndradeDivision of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, United States.
Aris BarasRegeneron Genetics Center, Tarrytown, New York, United States.
Julie HorowitzRegeneron Genetics Center, Tarrytown, New York, United States.
Manuel A R FerreiraRegeneron Genetics Center, Tarrytown, New York, United States.
Dylan SunRegeneron Genetics Center, Tarrytown, New York, United States.
David E JonesTranslational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
Steven FlackAcademic Department of Medical Genetics, University of Cambridge, Cambridge, United Kingdom.
Ann SpicerAcademic Department of Medical Genetics, University of Cambridge, Cambridge, United Kingdom.
Victoria L MulcahyAcademic Department of Medical Genetics, University of Cambridge, Cambridge, United Kingdom.
Jinyoung ByanInstitute for Clinical and Translational Research, Baylor College of Medicine, Houston, Texas, United States.
Younghun HanInstitute for Clinical and Translational Research, Baylor College of Medicine, Houston, Texas, United States.
Richard N SandfordAcademic Department of Medical Genetics, University of Cambridge, Cambridge, United Kingdom.
Konstantinos N LazaridisDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, United States.
Christopher I AmosInstitute for Clinical and Translational Research, Baylor College of Medicine, Houston, Texas, United States.
Gideon M HirschfieldToronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University of Toronto, Toronto, Ontario, Canada.
Michael F SeldinUniversity of California, Davis, California, United States.
Pietro InvernizziDivision of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza, Italy.
Katherine A SiminovitchDepartments of Medicine, Immunology and Medical Sciences, University of Toronto, Toronto, Ontario, Canada; Mount Sinai Hospital, Lunenfeld-Tanenbaum Research Institute and Toronto General Research Institute, Toronto, Ontario, Canada.
Xiong MaDivision of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai Institute of Digestive Disease, Shanghai, China.
Minoru NakamuraClinical Research Center, National Hospital Organization, Nagasaki Medical Center, Omura, Japan; Department of Hepatology, Nagasaki Graduate School of Biomedical Sciences, Japan.
George F MellsAcademic Department of Medical Genetics, University of Cambridge, Cambridge, United Kingdom. Electronic address: gfm26@cam.ac.uk.
PBC Consortia
Canadian PBC Consortium
Chinese PBC Consortium
Italian PBC Study Group
Japan-PBC-GWAS Consortium
US PBC Consortium
UK-PBC Consortium
University of Cambridge · GBMayo Clinic · USNewcastle University · GBNational Center for Global Health and Medicine · JPBaylor College of Medicine · USRegeneron (United States) · USUniversity of California, Davis · USAzienda Ospedaliera San Gerardo · ITThe University of Tokyo · JPMount Sinai Hospital · CANagasaki Medical Center · JPQingdao University · CNShanghai Jiao Tong University · CNKyoto University · JPUniversity of Toronto · CAHumanitas University · IT

Funding

Biotechnology and Biological Sciences Research Council BB/I025263/1Biotechnology and Biological Sciences Research Council BBI025751/1Biotechnology and Biological Sciences Research Council BB/M011186/1Department of HealthMedical Research Council 217065/Z/19/ZMedical Research Council G9815508Medical Research Council MC_PC_15018Medical Research Council MC_PC_19009Medical Research Council MR/L001489/1Wellcome TrustWellcome Trust 102858/Z/13/ZWellcome Trust WT088806
6 · The paper itself

Abstract

BACKGROUNDS &

aimsPrimary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intrahepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening.

methodsWe combined new and existing genotype data for 10,516 cases and 20,772 controls from 5 European and 2 East Asian cohorts.

resultsWe identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57

conclusionsThis study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders. LAY SUMMARY: Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10,516 people with PBC and 20,772 healthy individuals recruited in Canada, China, Italy, Japan, the UK, or the USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these 'candidate genes' to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC.

Indexed as

Genome-Wide Association StudyHumansLiver Cirrhosis, BiliaryALSPACERN RARE-LIVERGenomic co-localizationNetwork-based in silico drug efficacy screeningUK-PBC

Identifiers

PMID34033851
PMCPMC8811537
OpenAlexW3165249197

What Socratic 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 Socratic graph.