ArticlemedRxiv : the preprint server for health sciences2025
Germline Variants Influence Chronic Liver Disease Progression through Distinct Pathways.
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In one paragraph
Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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0citing papers in PubMed
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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.
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.
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Authors and funding
76 authors.
Marijana VujkovicCorporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.ORCID 0000-0003-4924-5714
David E KaplanCorporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.ORCID 0000-0002-3839-336X
Jonas GhouseThe Heart Centre, Laboratory for Molecular Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0002-9634-5964
Bao-Li LozaDepartment of Surgery, Penn Transplant Institute, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.ORCID 0000-0003-3917-6129
Joseph BrancaleDepartment of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, CT, USA.ORCID 0000-0002-1948-5103
Adam LewisDepartment of Biomedical Informatics, Center for Precision Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
David Y ZhangDepartment of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID 0000-0003-1377-9829
Michael G LevinCorporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.ORCID 0000-0002-9937-9932
Olivia J VeatchDepartment of Psychiatry and Behavioral Sciences, Division of Medical Informatics, University of Kansas Medical Center, Kansas City, KA, USA.ORCID 0000-0002-5509-7749
Josephine P JohnsonCorporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.ORCID 0009-0003-8962-1582
Carolin V SchneiderDepartment of Medicine III, Gastroenterology, Metabolic Diseases, and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany.ORCID 0000-0002-6728-9246
Anurag VermaCorporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.ORCID 0000-0002-5063-9107
Kirk J WangensteenDepartment of Internal Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.ORCID 0000-0001-6042-6490
Eleonora ScorlettiDepartment of Medicine, Division of Translational Medicine and Human Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID 0000-0002-7547-146X
Dipender GillDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.ORCID 0000-0001-7312-7078
Chigoziri KonkwoDepartment of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, CT, USA.ORCID 0000-0001-9082-7498
Alexis M GarófaloDepartment of Medicine, Division of Translational Medicine and Human Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Lindsay A GuareDepartment of Medicine, Division of Pathology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID 0000-0001-6988-5319
Tae-Wi Schwantes-AnDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID 0000-0001-6387-0095
Marco V AbreuDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID 0000-0002-5659-1255
Helene Gellert-KristensenDepartment of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.ORCID 0000-0002-9771-9876
Ole B PedersenDepartment of Clinical Immunology, Zealand University Hospital, Køge, Denmark.ORCID 0000-0003-2312-5976
Christian ErikstrupDepartment of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark.ORCID 0000-0001-6551-6647
Johan S BundgaardDepartment of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.ORCID 0000-0003-2069-9034
Erik SørensenDepartment of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.ORCID 0000-0002-5002-9077
Sisse R OstrowskiDepartment of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.ORCID 0000-0001-5288-3851
Henning BundgaardDepartment of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.ORCID 0000-0002-0563-7049
Kyung Min LeeVA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT, USA.
Abraham ShakedDepartment of Surgery, Penn Transplant Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID 0000-0002-2162-095X
Kim M OlthoffDepartment of Surgery, Penn Transplant Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID 0000-0001-5181-7502
Maarouf A HoteitDepartment of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID 0000-0001-6053-6884
Elizabeth K SpeliotesDepartment of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-1002-4140
Yanhua ChenDepartment of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA.
Antonino OliveriDepartment of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA.
Lishi YinDepartment of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA.
Luca Vc ValentiDepartment of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.ORCID 0000-0001-8909-0345
Francesco MalvestitiDepartment of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.ORCID 0000-0002-2430-5883
Daniele MarchelliDepartment of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.ORCID 0009-0004-9876-171X
Lorenzo MianoDepartment of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.ORCID 0009-0000-6552-2027
Quentin M AnsteeTranslational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.ORCID 0000-0002-9518-0088
Ann K DalyTranslational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.ORCID 0000-0002-8720-4190
Heather J CordellPopulation Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.ORCID 0000-0002-1879-5572
Rebecca DarlayPopulation Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.ORCID 0000-0002-7526-5527
Niek VerweijRegeneron Genetics Center, Regeneron Pharmaceuticals, Tarrytown, NY, USA.ORCID 0000-0002-4303-7685
George HindyRegeneron Genetics Center, Regeneron Pharmaceuticals, Tarrytown, NY, USA.ORCID 0000-0002-7257-9299
Adam LockeRegeneron Genetics Center, Regeneron Pharmaceuticals, Tarrytown, NY, USA.ORCID 0000-0001-6227-198X
Kentaro MatsuuraDepartment of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.ORCID 0000-0001-5906-6109
Sumeet K AsraniSimmons Transplant Institute, Baylor University Medical Center, Dallas, TX, USA.ORCID 0000-0001-9174-5670
Giuliano TestaSimmons Transplant Institute, Baylor University Medical Center, Dallas, TX, USA.ORCID 0000-0001-9535-9961
Luca A LottaRegeneron Genetics Center, Regeneron Pharmaceuticals, Tarrytown, NY, USA.
Marcus B JonesRegeneron Genetics Center, Regeneron Pharmaceuticals, Tarrytown, NY, USA.
Daniel R DochtermannCenter for Data and Computational Sciences (C-DACS), VA Boston Healthcare System, Boston, MA, USA.ORCID 0000-0001-9513-5124
Trina M Norden-KrichmarVA Long Beach Healthcare System, Long Beach, CA, USA.ORCID 0000-0002-0199-9915
Craig C TeerlinkVA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT, USA.ORCID 0000-0002-1992-2326
Poornima DevineniCenter for Data and Computational Sciences (C-DACS), VA Boston Healthcare System, Boston, MA, USA.
Saiju PyarajanCenter for Data and Computational Sciences (C-DACS), VA Boston Healthcare System, Boston, MA, USA.ORCID 0000-0002-9047-3762
Daniel J RaderDepartment of Medicine, Division of Translational Medicine and Human Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID 0000-0002-9245-9876
Yasuhito TanakaFaculty of Life Sciences, Department of Gastroenterology and Hepatology, Kumamoto University, Kumamoto, Japan.ORCID 0000-0002-2473-6966
Benjamin F VoightCorporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.ORCID 0000-0002-6205-9994
Silvia VilarinhoDepartment of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, CT, USA.ORCID 0000-0002-2099-4212
Lisa A BastaracheDepartment of Biomedical Informatics, Center for Precision Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID 0000-0003-3020-447X
Stefan StenderDepartment of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.ORCID 0000-0003-0281-5900
Philip S TsaoVA Palo Alto Healthcare System, Palo Alto, CA, USA.ORCID 0000-0001-7274-9318
Penn Medicine Biobank
DBDS Genomic Consortium
BioVU Biobank
Michigan Genomics Initiative
Regeneron Genetics Center
Indiana Biobank
All Of Us Research Program
Milano Biobank
LITMUS Consortium
VA Million Veteran Program
Timothy R MorganVA Long Beach Healthcare System, Long Beach, CA, USA.ORCID 0000-0003-1328-0307
Julie A LynchVA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT, USA.ORCID 0000-0003-0108-2127
Kyong-Mi ChangCorporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.ORCID 0000-0001-6811-9364
Funding
Technology to Empower Changes in Health (TECH) Network Participant Technologies CenterU24OD023176 · OD · SCRIPPS RESEARCH INSTITUTE, THE · PI TOPOL, ERIC JEFFREY · 2016 to 2022
$204.7MPrecision Medicine Initiative Cohort Program BiobankU24OD023121 · OD · MAYO CLINIC ROCHESTER · PI CEKANOVA, MARIA, CICEK, MINE · 2016 to 2024
$185.5MEnhancing All of Us Data Resources for Nutrition Precision Health: the All of Us Data and Research CenterU2COD023196 · OD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI GLAZER, DAVID, HARRIS, PAUL A. · 2016 to 2022
$143.7MVanderbilt Institute for Clinical and Translational Research (VICTR) -Identifying correlates of functional immunity in SARS-CoV-2 convalescent plasmaUL1TR002243 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Paul A. Harris, Wesley H Self · 2017 to 2026
$130.7MAdaptive Platform for Personalized EngagementU24OD023163 · OD · VIGNET, INC. · PI JAIN, PRADUMAN · 2017 to 2020
$102.6MUniversity of Arizona-Banner Health All of Us Research Program OT2OD026549 · OD · UNIVERSITY OF ARIZONA · PI MORENO, FRANCISCO A, REIMAN, ERIC MICHAEL · 2018 to 2023
$78.9MCalifornia Precision Medicine Research Program ConsortiumOT2OD026552 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ANTON-CULVER, HODA A, OHNO-MACHADO, LUCILA · 2018 to 2023
$73.4MAll of Us PennsylvaniaOT2OD026554 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E, VISWESWARAN, SHYAM · 2018 to 2023
$72.1MNew York City Consortium for Precision MedicineOT2OD026556 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BIER, LOUISE E, GHARAVI, ALI G · 2018 to 2023
$67.3MSouthEast Enrollment Center (SEEC) OT2OD026551 · OD · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI CARRASQUILLO, OLVEEN, COLON, VIVIAN · 2018 to 2023
$62.8MSouthern All of Us NetworkOT2OD026548 · OD · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI FOUAD, MONA N., KORF, BRUCE R · 2018 to 2023
$60.5MIllinois Precision Medicine Consortium OT2OD026557 · OD · NORTHWESTERN UNIVERSITY AT CHICAGO · PI AHSAN, HABIBUL, ARGOS, MARIA · 2018 to 2023
$60.5MBLRD VA I01 BX003362BLRD VA IK2 BX006551CSRD VA I01 CX002010NCATS NIH HHS UL1 TR002243NCATS NIH HHS UL1 TR002529NCRR NIH HHS C06 RR020128NHLBI NIH HHS F30 HL172382NIAID NIH HHS U01 AI152960NIDDK NIH HHS R01 DK128871NIDDK NIH HHS R01 DK131033NIDDK NIH HHS R01 DK131787NIDDK NIH HHS R01 DK134575NIDDK NIH HHS UM1 DK126194NIH HHS OT2 OD023205NIH HHS OT2 OD023206NIH HHS OT2 OD025276NIH HHS OT2 OD025277NIH HHS OT2 OD025315NIH HHS OT2 OD025337NIH HHS OT2 OD026548NIH HHS OT2 OD026549NIH HHS OT2 OD026550NIH HHS OT2 OD026551NIH HHS OT2 OD026552NIH HHS OT2 OD026553NIH HHS OT2 OD026554NIH HHS OT2 OD026555NIH HHS OT2 OD026556NIH HHS OT2 OD026557NIH HHS U24 OD023121NIH HHS U24 OD023163NIH HHS U24 OD023176NIH HHS U2C OD023196Wellcome Trust
Abstract
Cirrhosis and hepatocellular carcinoma (HCC) are long-term complications of chronic liver disease (CLD). In this large multi-ancestry genome-wide association study of all-cause cirrhosis (35,481 cases, 2.36M controls) and HCC (6,680 cases, 1.76M controls), we identified 27 loci associated with cirrhosis (10 novel) and 11 with HCC (three novel). Three novel cirrhosis loci were replicated in independent cohorts (e.g.
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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.