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Exome-wide association study of plasma lipids in >300,000 individuals.
Liu, Dajiang J; Peloso, Gina M; Yu, Haojie; Butterworth, Adam S; Wang, Xiao; Mahajan, Anubha; Saleheen, Danish; Emdin, Connor; Alam, Dewan; Alves, Alexessander Couto; Amouyel, Philippe; Di Angelantonio, Emanuele; Arveiler, Dominique; Assimes, Themistocles L; Auer, Paul L; Baber, Usman; Ballantyne, Christie M; Bang, Lia E; Benn, Marianne; Bis, Joshua C; Boehnke, Michael; Boerwinkle, Eric; Bork-Jensen, Jette; Bottinger, Erwin P; Brandslund, Ivan; Brown, Morris; Busonero, Fabio; Caulfield, Mark J; Chambers, John C; Chasman, Daniel I; Chen, Y Eugene; Chen, Yii-Der Ida; Chowdhury, Rajiv; Christensen, Cramer; Chu, Audrey Y; Connell, John M; Cucca, Francesco; Cupples, L Adrienne; Damrauer, Scott M; Davies, Gail; Deary, Ian J; Dedoussis, George; Denny, Joshua C; Dominiczak, Anna; Dubé, Marie-Pierre; Ebeling, Tapani; Eiriksdottir, Gudny; Esko, Tõnu; Farmaki, Aliki-Eleni; Feitosa, Mary F.
Afiliação
  • Liu DJ; Department of Public Health Sciences, Institute of Personalized Medicine, Penn State College of Medicine, Hershey, Pennsylvania, USA.
  • Peloso GM; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
  • Yu H; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
  • Butterworth AS; Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts, USA.
  • Wang X; MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Mahajan A; The National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Donor Health and Genomics at the University of Cambridge, Cambridge, UK.
  • Saleheen D; Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Emdin C; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Alam D; MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Alves AC; Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Amouyel P; Center for Non-Communicable Diseases, Karachi, Pakistan.
  • Di Angelantonio E; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
  • Arveiler D; Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
  • Assimes TL; ICDDR, B, Dhaka, Bangladesh.
  • Auer PL; Imperial College London, London, UK.
  • Baber U; Université Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE-Risk Factors and Molecular Determinants of Aging-related Diseases, Lille, France.
  • Ballantyne CM; MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Bang LE; The National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Donor Health and Genomics at the University of Cambridge, Cambridge, UK.
  • Benn M; Department of Epidemiology and Public Health, EA 3430, University of Strasbourg, Strasbourg, France.
  • Bis JC; VA Palo Alto Health Care System, Palo Alto, California, USA.
  • Boehnke M; Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
  • Boerwinkle E; Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
  • Bork-Jensen J; Cardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Bottinger EP; Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
  • Brandslund I; Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
  • Brown M; Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
  • Busonero F; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Caulfield MJ; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.
  • Chambers JC; Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.
  • Chasman DI; Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
  • Chen YE; Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
  • Chen YI; The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Chowdhury R; The Charles Bronfman Institute for Personalized Medicine, Ichan School of Medicine at Mount Sinai, New York, New York, USA.
  • Christensen C; Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark.
  • Chu AY; Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark.
  • Connell JM; Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • Cucca F; Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Monserrato, Cagliari, Italy.
  • Cupples LA; Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • Damrauer SM; The Barts Heart Centre, William Harvey Research Institute, Queen Mary University of London, London, UK.
  • Davies G; NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK.
  • Deary IJ; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
  • Dedoussis G; Department of Cardiology, Ealing Hospital NHS Trust, Southall, UK.
  • Denny JC; Imperial College Healthcare NHS Trust, London, UK.
  • Dominiczak A; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
  • Dubé MP; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
  • Ebeling T; Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan, USA.
  • Eiriksdottir G; The Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Departments of Pediatrics and Medicine, Los Angeles, California, USA.
  • Esko T; MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Farmaki AE; Medical Department, Lillebaelt Hospital, Vejle, Denmark.
  • Feitosa MF; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Nat Genet ; 49(12): 1758-1766, 2017 Dec.
Article em En | MEDLINE | ID: mdl-29083408
ABSTRACT
We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Variação Genética / Estudos de Associação Genética / Exoma / Lipídeos Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Variação Genética / Estudos de Associação Genética / Exoma / Lipídeos Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article