Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes.

Autor: Pazoki R; Department of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK. raha.pazoki@brunel.ac.uk.; 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., Vujkovic M; Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Elliott J; Department of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK.; Royal Surrey County Hospital, Guildford, Surrey, UK., Evangelou E; Department of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK.; Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece., Gill D; Department of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK.; British Heart Foundation Centre of Research Excellence, Imperial College London, London, UK., Ghanbari M; Department of Epidemiology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.; Department of Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran., van der Most PJ; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Pinto RC; Department of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK.; UK Dementia Research Institute, Imperial College London, London, UK., Wielscher M; Department of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK.; Department of Dermatology, Medical University of Vienna, Vienna, Austria., Farlik M; Department of Dermatology, Medical University of Vienna, Vienna, Austria., Zuber V; Department of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK., de Knegt RJ; Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands., Snieder H; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Uitterlinden AG; Department of Internal Medicine, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands., Lynch JA; VA Salt Lake City Health Care System, Salt Lake City, UT, USA.; University of Massachusetts, Boston, MA, USA., Jiang X; Division of Biomedical Sciences, Department of Life Sciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge, UK., Said S; Department of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK., Kaplan DE; Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Lee KM; VA Salt Lake City Health Care System, Salt Lake City, UT, USA.; School of Medicine, University of Utah, Salt Lake City, UT, USA., Serper M; Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Carr RM; Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Tsao PS; VA Palo Alto Health Care System, Palo Alto, CA, USA.; School of Medicine, Stanford University, Stanford, CA, USA., Atkinson SR; Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK., Dehghan A; Department of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK.; UK Dementia Research Institute, Imperial College London, London, UK., Tzoulaki I; Department of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK.; Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece., Ikram MA; Department of Epidemiology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands., Herzig KH; Institute of Biomedicine, Medical Research Center Oulu, Oulu University, Oulu, Finland.; Oulu University Hospital, Oulu, Finland.; Institute of Pediatrics, Poznan University of Medical Sciences, Poznan, Poland., Järvelin MR; Department of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK.; Center for Life Course Health Research, Faculty of Medicine, Oulu University, Oulu, Finland.; Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Uxbridge, UK.; Unit of Primary Care, Oulu University Hospital, Oulu, Finland., Alizadeh BZ; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., O'Donnell CJ; VA Boston Healthcare System, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; Brigham Women's Hospital, Boston, MA, USA., Saleheen D; Departments of Medicine and Cardiology, Columbia University, New York City, NY, USA., Voight BF; Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Chang KM; Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Thursz MR; Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK., Elliott P; Department of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, London, UK. p.elliott@imperial.ac.uk.; British Heart Foundation Centre of Research Excellence, Imperial College London, London, UK. p.elliott@imperial.ac.uk.; UK Dementia Research Institute, Imperial College London, London, UK. p.elliott@imperial.ac.uk.; National Institute for Health Research, Imperial Biomedical Research Centre, Imperial College London, London, UK. p.elliott@imperial.ac.uk.; Health Data Research UK at Imperial College London, London, UK. p.elliott@imperial.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 May 10; Vol. 12 (1), pp. 2579. Date of Electronic Publication: 2021 May 10.
DOI: 10.1038/s41467-021-22338-2
Abstrakt: 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.
Databáze: MEDLINE