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Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals.
Eicher, John D; Chami, Nathalie; Kacprowski, Tim; Nomura, Akihiro; Chen, Ming-Huei; Yanek, Lisa R; Tajuddin, Salman M; Schick, Ursula M; Slater, Andrew J; Pankratz, Nathan; Polfus, Linda; Schurmann, Claudia; Giri, Ayush; Brody, Jennifer A; Lange, Leslie A; Manichaikul, Ani; Hill, W David; Pazoki, Raha; Elliot, Paul; Evangelou, Evangelos; Tzoulaki, Ioanna; Gao, He; Vergnaud, Anne-Claire; Mathias, Rasika A; Becker, Diane M; Becker, Lewis C; Burt, Amber; Crosslin, David R; Lyytikäinen, Leo-Pekka; Nikus, Kjell; Hernesniemi, Jussi; Kähönen, Mika; Raitoharju, Emma; Mononen, Nina; Raitakari, Olli T; Lehtimäki, Terho; Cushman, Mary; Zakai, Neil A; Nickerson, Deborah A; Raffield, Laura M; Quarells, Rakale; Willer, Cristen J; Peloso, Gina M; Abecasis, Goncalo R; Liu, Dajiang J; Deloukas, Panos; Samani, Nilesh J; Schunkert, Heribert; Erdmann, Jeanette; Fornage, Myriam.
Afiliación
  • Eicher JD; Population Sciences Branch, National Heart Lung and Blood Institute, The Framingham Heart Study, Framingham, MA 01702, USA.
  • Chami N; Department of Medicine, Université de Montréal, Montréal, QC H3T 1J4, Canada; Montreal Heart Institute, Montréal, QC H1T 1C8, Canada.
  • Kacprowski T; Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald and Ernst-Mortiz-Arndt University Greifswald, Greifswald 17475, Germany; DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.
  • Nomura A; Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Medicine, Harvard Medi
  • Chen MH; Population Sciences Branch, National Heart Lung and Blood Institute, The Framingham Heart Study, Framingham, MA 01702, USA.
  • Yanek LR; Department of Medicine, Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Tajuddin SM; Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
  • Schick UM; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Genetics of Obesity and Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Slater AJ; Genetics, Target Sciences, GlaxoSmithKline, Research Triangle Park, NC 27709, USA; OmicSoft Corporation, Cary, NC 27513, USA.
  • Pankratz N; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55454, USA.
  • Polfus L; Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  • Schurmann C; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Genetics of Obesity and Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Giri A; Division of Epidemiology, Institute for Medicine and Public Health, Vanderbilt University, Nashville, TN 37235, USA.
  • Brody JA; Department of Medicine, University of Washington, Seattle, WA 98101, USA.
  • Lange LA; Department of Genetics, University of North Carolina, Chapel Hill, NC 27514, USA.
  • Manichaikul A; Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA.
  • Hill WD; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK; Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
  • Pazoki R; Department of Epidemiology, Erasmus MC, Rotterdam 3000, the Netherlands.
  • Elliot P; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK.
  • Evangelou E; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK; Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina 45110, Greece.
  • Tzoulaki I; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK; Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina 45110, Greece.
  • Gao H; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK.
  • Vergnaud AC; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK.
  • Mathias RA; Department of Medicine, Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Divisions of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Becker DM; Department of Medicine, Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Becker LC; Department of Medicine, Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Divisions of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Burt A; Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
  • Crosslin DR; Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, WA 98105, USA.
  • Lyytikäinen LP; Department of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland; Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere 33514, Finland.
  • Nikus K; Department of Cardiology, Heart Center, Tampere University Hospital, Tampere 33521, Finland; University of Tampere, School of Medicine, Tampere 33514, Finland.
  • Hernesniemi J; Department of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland; Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere 33514, Finland; Department of Cardiology, Heart Center, Tampere University Hospital, Tampere 33521, Finland.
  • Kähönen M; Department of Clinical Physiology, Tampere University Hospital, Tampere 33521, Finland; Department of Clinical Physiology, University of Tampere, Tampere 33514, Finland.
  • Raitoharju E; Department of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland; Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere 33514, Finland.
  • Mononen N; Department of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland; Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere 33514, Finland.
  • Raitakari OT; Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku 20521, Finland; Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku 20520, Finland.
  • Lehtimäki T; Department of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland; Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere 33514, Finland.
  • Cushman M; Departments of Medicine and Pathology, University of Vermont College of Medicine, Burlington, VT 05405, USA.
  • Zakai NA; Departments of Medicine and Pathology, University of Vermont College of Medicine, Burlington, VT 05405, USA.
  • Nickerson DA; Department of Genome Sciences, University of Washington, Seattle, WA 98105, USA.
  • Raffield LM; Department of Genetics, University of North Carolina, Chapel Hill, NC 27514, USA.
  • Quarells R; Morehouse School of Medicine, Social Epidemiology Research Center, Cardiovascular Research Institute, Atlanta, GA 30310, USA.
  • Willer CJ; Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI 48108, USA; Department of Computational Medicine and Bioinformatics, Department of Human Genetics, University of Michigan, Ann Arbor, MI 48108, USA; Department of Biostatistics, University of
  • Peloso GM; Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
  • Abecasis GR; Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI 48108, USA.
  • Liu DJ; Department of Public Health Sciences, College of Medicine, Pennsylvania State University, Hershey, PA 17033, USA.
  • Deloukas P; William Harvey Research Institute, Queen Mary University London, London E1 4NS, UK; Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  • Samani NJ; Department of Cardiovascular Sciences, University of Leicester, Leicester LE1 7RH, UK; NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK.
  • Schunkert H; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich 80333, Germany; Deutsches Herzzentrum München, Technische Universität München, Munich 80333, Germany.
  • Erdmann J; Institute for Integrative and Experimental Genomics, University of Lübeck, Lübeck 23562, Germany; DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel, Lübeck 23562, Germany.
  • Fornage M; Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Am J Hum Genet ; 99(1): 40-55, 2016 Jul 07.
Article en En | MEDLINE | ID: mdl-27346686
ABSTRACT
Platelet production, maintenance, and clearance are tightly controlled processes indicative of platelets' important roles in hemostasis and thrombosis. Platelets are common targets for primary and secondary prevention of several conditions. They are monitored clinically by complete blood counts, specifically with measurements of platelet count (PLT) and mean platelet volume (MPV). Identifying genetic effects on PLT and MPV can provide mechanistic insights into platelet biology and their role in disease. Therefore, we formed the Blood Cell Consortium (BCX) to perform a large-scale meta-analysis of Exomechip association results for PLT and MPV in 157,293 and 57,617 individuals, respectively. Using the low-frequency/rare coding variant-enriched Exomechip genotyping array, we sought to identify genetic variants associated with PLT and MPV. In addition to confirming 47 known PLT and 20 known MPV associations, we identified 32 PLT and 18 MPV associations not previously observed in the literature across the allele frequency spectrum, including rare large effect (FCER1A), low-frequency (IQGAP2, MAP1A, LY75), and common (ZMIZ2, SMG6, PEAR1, ARFGAP3/PACSIN2) variants. Several variants associated with PLT/MPV (PEAR1, MRVI1, PTGES3) were also associated with platelet reactivity. In concurrent BCX analyses, there was overlap of platelet-associated variants with red (MAP1A, TMPRSS6, ZMIZ2) and white (PEAR1, ZMIZ2, LY75) blood cell traits, suggesting common regulatory pathways with shared genetic architecture among these hematopoietic lineages. Our large-scale Exomechip analyses identified previously undocumented associations with platelet traits and further indicate that several complex quantitative hematological, lipid, and cardiovascular traits share genetic factors.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Variación Genética / Plaquetas / Exoma Tipo de estudio: Prognostic_studies / Systematic_reviews Límite: Female / Humans / Male Idioma: En Revista: Am J Hum Genet Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Variación Genética / Plaquetas / Exoma Tipo de estudio: Prognostic_studies / Systematic_reviews Límite: Female / Humans / Male Idioma: En Revista: Am J Hum Genet Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos