ArticleNature communications2021
Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes.
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Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 6 of them syntheses that pooled it.
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86citing papers in PubMed, 6 pooled it
13.0field-weighted citation impact, top 1% of its field
What it found
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Who cites it
86 citing papers in PubMed, 6 syntheses or guidelines pooled it, 125 citations in OpenAlex.
- Skeletal muscle eQTL meta-analysis implicates genes in the genetic architecture of muscular and cardiometabolic traits.American journal of human genetics · 2025Pooled it
- Investigating the shared genetic information between serum concentration levels of liver enzymes and cholelithiasis.BMC gastroenterology · 2025Pooled it
- Discovery of novel ancestry specific genes for androgens and hypogonadism in Million Veteran Program Men.Nature communications · 2025Pooled it
- Serum liver enzymes and risk of stroke: Systematic review with meta-analyses and Mendelian randomization studies.European journal of neurology · 2024Pooled it
- Liver eQTL meta-analysis illuminates potential molecular mechanisms of cardiometabolic traits.American journal of human genetics · 2024Pooled it
- A genome-wide meta-analysis identifies 50 genetic loci associated with carpal tunnel syndrome.Nature communications · 2022Pooled it
- Genetic Variants Associated With the Biochemical Response to Vitamin D3 in the Multi-Ethnic Study of Atherosclerosis.The Journal of clinical endocrinology and metabolism · 2025Trial
- Refining Genetic Instruments for Dietary Intake Mendelian Randomization Using Phenome-Wide Association Studies.Genetic epidemiology · 2026Article
- Excessive EFHD1-dependent ER-mitochondrial contacts drive a maladaptive antiviral response in metabolic liver disease.The Journal of clinical investigation · 2026Article
- Polymorphic Variant Associated with Sex Hormone-Binding Globulin Level Is a Risk Factor for Preeclampsia.International journal of molecular sciences · 2026Article
- Exploring the role of inflammatory cytokines in obesity-mediated MASLD development and drug target identification.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- MIXPRS enables multi-population and multi-method polygenic risk scores using summary statistics.Nature genetics · 2026Article
- Association of ACE I/D polymorphism with blood pressure response to valsartan-hydrochlorothiazide combination therapy in hypertensive patients from Khyber Pakhtunkhwa, Pakistan.Pharmacogenomics · 2026Observational
- Selection-guided discovery in South Asians implicates the MAPT locus in insulin resistance.medRxiv : the preprint server for health sciences · 2026Article
- Massively parallel reporter assay-informed modeling improves prediction of context-specific enhancer-gene regulatory interactions.Nucleic acids research · 2026Article
- A Modular Bioinstructive Platform Reveals Mechanistic Insights into Additive-Free, Topography-Driven Osteogenesis.Advanced healthcare materials · 2026Article
- Mapping epigenetic gene variant dynamics: comparative analysis of frequency, functional impact and trait associations in African and European populations.Scientific reports · 2026Article
- Unravelling genetic susceptibility and causal factors in liver health using MRI quantification of inflammation, fat and iron in the liver.Human genomics · 2026Article
- Excessive CabioRxiv : the preprint server for biology · 2026Article
- Genetic associations of circulating plasma proteins with cardiometabolic diseases.Genome biology · 2026Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
37 authors at 20 institutions in 8 countries.
Raha Pazoki *Department of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK. raha.pazoki@brunel.ac.uk.ORCID http://orcid.org/0000-0002-5142-2348
Marijana Vujkovic *Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-4924-5714
Joshua ElliottDepartment of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK.
Evangelos EvangelouDepartment of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK.ORCID http://orcid.org/0000-0002-5488-2999
Dipender GillDepartment of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK.ORCID http://orcid.org/0000-0001-7312-7078
Mohsen GhanbariDepartment of Epidemiology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0002-9476-7143
Peter J van der MostDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.ORCID http://orcid.org/0000-0001-8450-3518
Rui Climaco PintoDepartment of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK.
Matthias WielscherDepartment of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK.
Matthias FarlikDepartment of Dermatology, Medical University of Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0003-0698-2992
Verena ZuberDepartment of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK.ORCID http://orcid.org/0000-0001-9827-1877
Robert J de KnegtDepartment of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
Harold SniederDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.ORCID http://orcid.org/0000-0003-1949-2298
André G UitterlindenDepartment of Internal Medicine, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0002-7276-3387
Lifelines Cohort Study
Julie A LynchVA Salt Lake City Health Care System, Salt Lake City, UT, USA.ORCID http://orcid.org/0000-0003-0108-2127
Xiyun JiangDivision of Biomedical Sciences, Department of Life Sciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge, UK.
Saredo SaidDepartment of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK.
David E KaplanCorporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
Kyung Min LeeVA Salt Lake City Health Care System, Salt Lake City, UT, USA.ORCID http://orcid.org/0000-0001-8995-0448
Marina SerperCorporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
Rotonya M CarrCorporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-0235-6994
Philip S TsaoVA Palo Alto Health Care System, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0001-7274-9318
Stephen R AtkinsonDivision of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK.
Abbas DehghanDepartment of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK.
Ioanna TzoulakiDepartment of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK.ORCID http://orcid.org/0000-0002-4275-9328
M Arfan IkramDepartment of Epidemiology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0003-0372-8585
Karl-Heinz HerzigInstitute of Biomedicine, Medical Research Center Oulu, Oulu University, Oulu, Finland.
Marjo-Riitta JärvelinDepartment of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK.ORCID http://orcid.org/0000-0002-2149-0630
Behrooz Z AlizadehDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.ORCID http://orcid.org/0000-0002-1415-8007
Christopher J O'DonnellVA Boston Healthcare System, Boston, MA, USA.ORCID http://orcid.org/0000-0002-2667-8624
Danish SaleheenDepartments of Medicine and Cardiology, Columbia University, New York City, NY, USA.ORCID http://orcid.org/0000-0001-6193-020X
Benjamin F Voight *Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-6205-9994
Kyong-Mi Chang *Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-6811-9364
Mark R Thursz *Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK.
Paul Elliott *Department of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK. p.elliott@imperial.ac.uk.ORCID http://orcid.org/0000-0002-7511-5684
VA Million Veteran Program
VA Boston Healthcare System · USUniversity Medical Center Groningen · NLPhiladelphia VA Medical Center · USVA Connecticut Healthcare System · USMRC Centre for Environment and HealthRaymond G. Murphy VA Medical Center · USUniversity of Ioannina · GRVA Salt Lake City Healthcare System · USBrigham and Women's Hospital · USBritish Heart Foundation · GBColumbia VA Health Care System · USEdith Nourse Rogers Memorial Veterans Hospital · USEdward Hines, Jr. VA Hospital · USErasmus MC · NLFayetteville VA Medical Center · USHampton VA Medical Center · USHunter Holmes McGuire VA Medical Center · USJames A. Haley Veterans' Hospital · USLouisville VA Medical Center · USMaineHealth · US
Funding
Genetics of cardiovascular risk factors in large founder population birth controlR01HL087679 · NHLBI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI HIRSCHHORN, JOEL N · 2007 to 2009
$4.0MNetwork-based algorithms for target identification and drug repositioning from genetic associationsR01HG010067 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI GREENE, CASEY S · 2018 to 2022
$3.2MMolecular Mechanisms Of Post-Transplant Recurrent Alcoholic Liver DiseaseR01AA026302 · NIAAA · UNIVERSITY OF WASHINGTON · PI ROTONYA M CARR · 2017 to 2026
$3.2MAlgorithms to identify non-coding mutational burden and disease-relevant pathwaysR01DK101478 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI VOIGHT, BENJAMIN FRANKLIN · 2014 to 2018
$2.9MWhole Genome Assoc. Analysis Strategies for Multi. PhenotypesRL1MH083268 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FREIMER, NELSON B. · 2007 to 2011
$2.1MDeveloping technology-based approaches to improve access and quality of care in cirrhosisK23DK115897 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI SERPER, MARINA · 2018 to 2022
$961kAlgorithms to identify non-coding mutational burden and disease-relevant pathwaysR56DK101478 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI VOIGHT, BENJAMIN FRANKLIN · 2019 to 2019
$272kBLRD VA I01 BX003362British Heart Foundation SP/13/2/30111Department of HealthMedical Research Council MC_PC_17228Medical Research Council MC_QA137853Medical Research Council MR/L01341X/1Medical Research Council MR/L01632X/1Medical Research Council MR/R023484/1Medical Research Council MR/R0265051/1Medical Research Council MR/R026505/2Medical Research Council MR/S019669/1Medical Research Council MR/S03658X/1NHGRI NIH HHS R01 HG010067NHLBI NIH HHS R01 HL087679NIAAA NIH HHS R01 AA026302NIDDK NIH HHS K23 DK115897NIDDK NIH HHS R01 DK101478NIDDK NIH HHS R56 DK101478NIMH NIH HHS RL1 MH083268
Abstract
Serum concentration of hepatic enzymes are linked to liver dysfunction, metabolic and cardiovascular diseases. We perform genetic analysis on serum levels of alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) using data on 437,438 UK Biobank participants. Replication in 315,572 individuals from European descent from the Million Veteran Program, Rotterdam Study and Lifeline study confirms 517 liver enzyme SNPs. Genetic risk score analysis using the identified SNPs is strongly associated with serum activity of liver enzymes in two independent European descent studies (The Airwave Health Monitoring study and the Northern Finland Birth Cohort 1966). Gene-set enrichment analysis using the identified SNPs highlights involvement in liver development and function, lipid metabolism, insulin resistance, and vascular formation. Mendelian randomization analysis shows association of liver enzyme variants with coronary heart disease and ischemic stroke. Genetic risk score for elevated serum activity of liver enzymes is associated with higher fat percentage of body, trunk, and liver and body mass index. Our study highlights the role of molecular pathways regulated by the liver in metabolic disorders and cardiovascular disease.
Indexed as
AgedAlanine TransaminaseAlkaline PhosphataseCardiovascular DiseasesCohort StudiesDatabases, GeneticFemalegamma-GlutamyltransferaseGene Expression Regulation, EnzymologicGenetic Predisposition to DiseaseGenetic TestingGenome-Wide Association StudyHumansInsulin ResistanceLipid MetabolismLiverAlanine TransaminaseAlkaline Phosphatasegamma-Glutamyltransferase
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