ArticleNature genetics2024
Integrative common and rare variant analyses provide insights into the genetic architecture of liver cirrhosis.
Open access · hybridAbstract read
In one paragraph
Article in Nature genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 1 pooled it
18.9field-weighted citation impact, top 1% of its field
What it found
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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.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Meta-Analysis: Redefining Liver Disease Risk in Heterozygous Alpha-1 Antitrypsin Deficiency.Alimentary pharmacology & therapeutics · 2026Pooled it
- Refining Genetic Instruments for Dietary Intake Mendelian Randomization Using Phenome-Wide Association Studies.Genetic epidemiology · 2026Article
- Age-Specific Associations of Polygenic Risk Scores With Advanced Fibrosis and Histological Activity in Biopsy-Proven MASLD.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Subtyping metabolic dysfunction-associated steatotic liver disease using electronic health record-linked genomic cohorts reveals diverse etiologies and progression.Nature communications · 2026Article
- Genetic testing in liver diseases: Clinical applications.JHEP reports : innovation in hepatology · 2026Review
- The dynamic spectrum of steatotic liver disease: the global perspective.Nature reviews. Gastroenterology & hepatology · 2026Review
- Rare Germline Variants in Key Pathways Contribute to Hepatocellular Carcinoma Risk in Hispanic Individuals.Cancers · 2026Article
- Shared mechanisms of organ fibrosis.JCI insight · 2026Review
- Review
- Multi-ancestry genome-wide association meta-analysis of hepatocellular carcinoma identifies 15 risk loci including MAP3K9, DHRS1, MTTP, and 8q24.21.HGG advances · 2026Article
- Genome-wide association study of untargeted plasma metabolomic profiles identifies host genetic regulation in people with HIV.HGG advances · 2026Article
- Germline mutations and somatic mosaicism in steatotic liver diseases and related liver carcinogenesis.Nature reviews. Gastroenterology & hepatology · 2026Review
- Observational
- Marine Bioactives in Liver Aging: Mechanistic Insights and Translational Potential.Marine drugs · 2026Review
- Toward a Genomics-Driven Hepatology: Liver Biology, Precision Diagnosis, and the Rise in Genetic Therapies.Pharmaceutics · 2026Review
- TheJHEP reports : innovation in hepatology · 2026Article
- Disentangling the Effect of BMI on Hepatocellular Carcinoma From Cirrhosis With Multivariable Mendelian Randomization.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Human Genetic Analysis Reveals Circulating Alpha-1 Antitrypsin Level as a Protective Factor in Sepsis.medRxiv : the preprint server for health sciences · 2026Article
- Robust human genetic evidence supporting causal effects of FGF21 on reducing alcohol consuming behaviours.BMC medicine · 2026Article
- Deciphering casual association between brain structure and liver cirrhosis: Insights from Mendelian randomization.Medicine · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
56 authors at 20 institutions in 4 countries.
Jonas GhouseDepartment of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. jonasghouse@gmail.com.ORCID http://orcid.org/0000-0002-9634-5964
Gardar SveinbjörnssondeCODE Genetics/Amgen, Reykjavik, Iceland.ORCID http://orcid.org/0000-0003-2429-9468
Marijana VujkovicCorporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-4924-5714
Anne-Sofie SeidelinDepartment of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Helene Gellert-KristensenDepartment of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-9771-9876
Gustav AhlbergCardiac Genetics Group, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0003-0066-2779
Vinicius TragantedeCODE Genetics/Amgen, Reykjavik, Iceland.ORCID http://orcid.org/0000-0002-8223-8957
Søren A RandDepartment of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-1892-1911
Joseph BrancaleSection of Digestive Diseases, Department of Internal Medicine, and Department of Pathology, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-1948-5103
Silvia VilarinhoSection of Digestive Diseases, Department of Internal Medicine, and Department of Pathology, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-2099-4212
Pia Rengtved LundegaardCardiac Genetics Group, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-8284-1844
Erik SørensenDepartment of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Christian ErikstrupDepartment of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark.ORCID http://orcid.org/0000-0001-6551-6647
Mie Topholm BruunDepartment of Clinical Immunology, Odense University Hospital, Odense, Denmark.ORCID http://orcid.org/0000-0002-8819-5388
Bitten Aagaard JensenDepartment of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark.
Søren BrunakTranslational Disease Systems Biology, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0003-0316-5866
Karina BanasikDepartment of Obstetrics and Gynaecology, Copenhagen University Hospital Hvidovre, Copenhagen, Denmark.ORCID http://orcid.org/0000-0003-2489-2499
Henrik UllumStatens Serum Institut, Copenhagen, Denmark.
DBDS Genomic Consortium
Niek VerweijRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Luca LottaRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.ORCID http://orcid.org/0000-0002-2619-5956
Aris BarasRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.ORCID http://orcid.org/0000-0002-6830-3396
Regeneron Genetics Center
Tooraj MirshahiDepartment of Molecular and Functional Genomics, Geisinger Health System, Danville, PA, USA.ORCID http://orcid.org/0000-0002-0754-3820
David J CareyDepartment of Molecular and Functional Genomics, Geisinger Health System, Danville, PA, USA.
Geisinger-Regeneron DiscovEHR Collaboration
VA Million Veteran Program
David E KaplanCorporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-3839-336X
Julie LynchVA Informatics and Computing Infrastructure (VINCI), VA Salt Lake City Health Care System, Salt Lake City, UT, USA.ORCID http://orcid.org/0000-0003-0108-2127
Timothy MorganGastroenterology Section, Veterans Affairs Long Beach Healthcare System, Long Beach, CA, USA.
Tae-Hwi Schwantes-AnGastroenterology Section, Veterans Affairs Long Beach Healthcare System, Long Beach, CA, USA.
Daniel R DochtermannCenter for Data and Computational Sciences, VA Boston Healthcare System, Boston, MA, USA.
Saiju PyarajanCenter for Data and Computational Sciences, VA Boston Healthcare System, Boston, MA, USA.
Philip S TsaoPalo Alto Epidemiology Research and Information Center for Genomics, VA Palo Alto, Palo Alto, CA, USA.
Estonian Biobank Research Team
Triin LaiskEstonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.ORCID http://orcid.org/0000-0003-1501-9030
Reedik MägiEstonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Julia KozlitinaEugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0001-7720-2290
Anne Tybjærg-HansenDepartment of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
David JonesPrecision Genomics, Intermountain Healthcare, Saint George, UT, USA.
Kirk U KnowltonIntermountain Medical Center, Intermountain Heart Institute, Salt Lake City, UT, USA.
Lincoln NadauldPrecision Genomics, Intermountain Healthcare, Saint George, UT, USA.
Egil FerkingstaddeCODE Genetics/Amgen, Reykjavik, Iceland.ORCID http://orcid.org/0000-0001-8090-7988
Einar S BjörnssonFaculty of Medicine, University of Iceland, Reykjavik, Iceland.
Magnus O UlfarssondeCODE Genetics/Amgen, Reykjavik, Iceland.
Árni SturlusondeCODE Genetics/Amgen, Reykjavik, Iceland.
Patrick SulemdeCODE Genetics/Amgen, Reykjavik, Iceland.ORCID http://orcid.org/0000-0001-7123-6123
Ole B PedersenDepartment of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0003-2312-5976
Sisse R OstrowskiDepartment of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.ORCID http://orcid.org/0000-0001-5288-3851
Daniel F GudbjartssondeCODE Genetics/Amgen, Reykjavik, Iceland.ORCID http://orcid.org/0000-0002-5222-9857
Kari StefanssondeCODE Genetics/Amgen, Reykjavik, Iceland.ORCID http://orcid.org/0000-0003-1676-864X
Morten Salling OlesenDepartment of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.ORCID http://orcid.org/0000-0001-9477-5322
Kyong-Mi ChangCorporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
Hilma HolmdeCODE Genetics/Amgen, Reykjavik, Iceland.ORCID http://orcid.org/0000-0002-9517-6636
Henning BundgaardDepartment of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Stefan StenderDepartment of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. stefan.stender@regionh.dk.ORCID http://orcid.org/0000-0003-0281-5900
University of Copenhagen · DKdeCODE Genetics (Iceland) · ISCopenhagen University Hospital · DKIntermountain Healthcare · USRegeneron (United States) · USGeisinger Health System · USUniversity of Tartu · EEVA Boston Healthcare System · USYale University · USAalborg University Hospital · DKAarhus University Hospital · DKBrigham and Women's Hospital · USOdense University Hospital · DKPhiladelphia VA Medical Center · USSouthwestern Medical Center · USStatens Serum Institut · DKSteno Diabetes Centers · DKUniversity of California, Irvine · USUniversity of Iceland · ISUniversity of Pennsylvania · US
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
$143.7MYale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MAdaptive 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 BX003362NCATS NIH HHS UL1 TR001863NIDDK NIH HHS K08 DK113109NIDDK NIH HHS R01 DK090066NIDDK NIH HHS R01 DK131033NIDDK NIH HHS R01 DK134575NIGMS NIH HHS T32 GM136651NIH 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 OD023196
Abstract
We report a multi-ancestry genome-wide association study on liver cirrhosis and its associated endophenotypes, alanine aminotransferase (ALT) and γ-glutamyl transferase. Using data from 12 cohorts, including 18,265 cases with cirrhosis, 1,782,047 controls, up to 1 million individuals with liver function tests and a validation cohort of 21,689 cases and 617,729 controls, we identify and validate 14 risk associations for cirrhosis. Many variants are located near genes involved in hepatic lipid metabolism. One of these, PNPLA3 p.Ile148Met, interacts with alcohol intake, obesity and diabetes on the risk of cirrhosis and hepatocellular carcinoma (HCC). We develop a polygenic risk score that associates with the progression from cirrhosis to HCC. By focusing on prioritized genes from common variant analyses, we find that rare coding variants in GPAM associate with lower ALT, supporting GPAM as a potential target for therapeutic inhibition. In conclusion, this study provides insights into the genetic underpinnings of cirrhosis.
Indexed as
Genetic Predisposition to DiseaseGenome-Wide Association StudyLiver CirrhosisAlanine TransaminaseCarcinoma, HepatocellularCase-Control StudiesCohort StudiesFemalegamma-GlutamyltransferaseGenetic VariationHumansLipaseLiver NeoplasmsMaleMembrane ProteinsMultifactorial InheritanceAlanine Transaminasegamma-GlutamyltransferaseLipaseMembrane Proteins
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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 Socratic graph.