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Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes.
Pazoki, Raha; Vujkovic, Marijana; Elliott, Joshua; Evangelou, Evangelos; Gill, Dipender; Ghanbari, Mohsen; van der Most, Peter J; Pinto, Rui Climaco; Wielscher, Matthias; Farlik, Matthias; Zuber, Verena; de Knegt, Robert J; Snieder, Harold; Uitterlinden, André G; Lynch, Julie A; Jiang, Xiyun; Said, Saredo; Kaplan, David E; Lee, Kyung Min; Serper, Marina; Carr, Rotonya M; Tsao, Philip S; Atkinson, Stephen R; Dehghan, Abbas; Tzoulaki, Ioanna; Ikram, M Arfan; Herzig, Karl-Heinz; Järvelin, Marjo-Riitta; Alizadeh, Behrooz Z; O'Donnell, Christopher J; Saleheen, Danish; Voight, Benjamin F; Chang, Kyong-Mi; Thursz, Mark R; Elliott, Paul.
Affiliation
  • Pazoki R; Department of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK. raha.pazoki@brunel.ac.uk.
  • Vujkovic M; Division of Biomedical Sciences, Department of Life Sciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge, UK. raha.pazoki@brunel.ac.uk.
  • Elliott J; Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
  • Evangelou E; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Gill D; Department of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK.
  • Ghanbari M; Royal Surrey County Hospital, Guildford, Surrey, UK.
  • van der Most PJ; Department of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK.
  • Pinto RC; Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.
  • Wielscher M; Department of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK.
  • Farlik M; British Heart Foundation Centre of Research Excellence, Imperial College London, London, UK.
  • Zuber V; Department of Epidemiology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
  • de Knegt RJ; Department of Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
  • Snieder H; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Uitterlinden AG; Department of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK.
  • Lynch JA; Department of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK.
  • Jiang X; Department of Dermatology, Medical University of Vienna, Vienna, Austria.
  • Said S; Department of Dermatology, Medical University of Vienna, Vienna, Austria.
  • Kaplan DE; Department of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK.
  • Lee KM; Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
  • Serper M; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Carr RM; Department of Internal Medicine, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
  • Atkinson SR; VA Salt Lake City Health Care System, Salt Lake City, UT, USA.
  • Dehghan A; University of Massachusetts, Boston, MA, USA.
  • Tzoulaki I; Division of Biomedical Sciences, Department of Life Sciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge, UK.
  • Ikram MA; Department of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK.
  • Herzig KH; Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
  • Järvelin MR; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Alizadeh BZ; VA Salt Lake City Health Care System, Salt Lake City, UT, USA.
  • O'Donnell CJ; School of Medicine, University of Utah, Salt Lake City, UT, USA.
  • Saleheen D; Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
  • Voight BF; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Chang KM; Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
  • Thursz MR; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Elliott P; VA Palo Alto Health Care System, Palo Alto, CA, USA.
Nat Commun ; 12(1): 2579, 2021 05 10.
Article in En | MEDLINE | ID: mdl-33972514
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cardiovascular Diseases / Alanine Transaminase / Alkaline Phosphatase / Gamma-Glutamyltransferase / Liver / Metabolic Diseases Type of study: Clinical_trials / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Aged / Female / Humans / Male / Middle aged Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2021 Document type: Article Country of publication: United kingdom
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cardiovascular Diseases / Alanine Transaminase / Alkaline Phosphatase / Gamma-Glutamyltransferase / Liver / Metabolic Diseases Type of study: Clinical_trials / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Aged / Female / Humans / Male / Middle aged Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2021 Document type: Article Country of publication: United kingdom