Your browser doesn't support javascript.
loading
Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks.
Peloso, Gina M; Auer, Paul L; Bis, Joshua C; Voorman, Arend; Morrison, Alanna C; Stitziel, Nathan O; Brody, Jennifer A; Khetarpal, Sumeet A; Crosby, Jacy R; Fornage, Myriam; Isaacs, Aaron; Jakobsdottir, Johanna; Feitosa, Mary F; Davies, Gail; Huffman, Jennifer E; Manichaikul, Ani; Davis, Brian; Lohman, Kurt; Joon, Aron Y; Smith, Albert V; Grove, Megan L; Zanoni, Paolo; Redon, Valeska; Demissie, Serkalem; Lawson, Kim; Peters, Ulrike; Carlson, Christopher; Jackson, Rebecca D; Ryckman, Kelli K; Mackey, Rachel H; Robinson, Jennifer G; Siscovick, David S; Schreiner, Pamela J; Mychaleckyj, Josyf C; Pankow, James S; Hofman, Albert; Uitterlinden, Andre G; Harris, Tamara B; Taylor, Kent D; Stafford, Jeanette M; Reynolds, Lindsay M; Marioni, Riccardo E; Dehghan, Abbas; Franco, Oscar H; Patel, Aniruddh P; Lu, Yingchang; Hindy, George; Gottesman, Omri; Bottinger, Erwin P; Melander, Olle.
Afiliação
  • Peloso GM; Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Program in Medical and Population Genetics, Broad In
  • Auer PL; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI 53201, USA.
  • Bis JC; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA.
  • Voorman A; Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
  • Morrison AC; Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  • Stitziel NO; Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Brody JA; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA.
  • Khetarpal SA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Crosby JR; Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Department of Biostatistics, Bioinformatics, and Systems Biology, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA.
  • Fornage M; Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  • Isaacs A; Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam 3015CN, the Netherlands.
  • Jakobsdottir J; Icelandic Heart Association, Kopavogur 201, Iceland.
  • Feitosa MF; Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Davies G; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK; Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
  • Huffman JE; MRC Human Genetics, MRC IGMM, University of Edinburgh, Edinburgh EH4 2XU, UK.
  • Manichaikul A; Center for Public Health Genomics and Department of Public Health Sciences, University of Virginia, Charlottesville, VA 22908, USA.
  • Davis B; Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  • Lohman K; Wake Forest School of Medicine, Winston-Salem, NC 27106, USA.
  • Joon AY; Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  • Smith AV; Icelandic Heart Association, Kopavogur 201, Iceland; Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland.
  • Grove ML; Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  • Zanoni P; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Redon V; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Demissie S; Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA; National Heart, Lung, and Blood Institute (NHLBI) Framingham Heart Study, Framingham, MA 01702, USA.
  • Lawson K; Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  • Peters U; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Carlson C; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Jackson RD; Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA.
  • Ryckman KK; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA 52242, USA.
  • Mackey RH; Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
  • Robinson JG; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA 52242, USA.
  • Siscovick DS; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA; Department of Epidemiology, University of Washington, Seattle, WA 98195, USA.
  • Schreiner PJ; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN 55454, USA.
  • Mychaleckyj JC; Center for Public Health Genomics and Department of Public Health Sciences, University of Virginia, Charlottesville, VA 22908, USA.
  • Pankow JS; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN 55454, USA.
  • Hofman A; Department of Epidemiology, Erasmus University Medical Center, Rotterdam 3015CN, the Netherlands.
  • Uitterlinden AG; Department of Epidemiology, Erasmus University Medical Center, Rotterdam 3015CN, the Netherlands.
  • Harris TB; National Institute on Aging, NIH, Bethesda, MD 20892, USA.
  • Taylor KD; Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
  • Stafford JM; Wake Forest School of Medicine, Winston-Salem, NC 27106, USA.
  • Reynolds LM; Wake Forest School of Medicine, Winston-Salem, NC 27106, USA.
  • Marioni RE; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK; Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
  • Dehghan A; Department of Epidemiology, Erasmus University Medical Center, Rotterdam 3015CN, the Netherlands.
  • Franco OH; Department of Epidemiology, Erasmus University Medical Center, Rotterdam 3015CN, the Netherlands.
  • Patel AP; Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA; School of Medicine, Yale University, New Haven, CT 06510, USA.
  • Lu Y; The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Hindy G; Department of Clinical Sciences in Malmö, Lund University, Clinical Research Center, Malmö 20502, Sweden.
  • Gottesman O; The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Bottinger EP; The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Melander O; Department of Clinical Sciences in Malmö, Lund University, Clinical Research Center, Malmö 20502, Sweden.
Am J Hum Genet ; 94(2): 223-32, 2014 Feb 06.
Article em En | MEDLINE | ID: mdl-24507774
ABSTRACT
Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncertain whether the PCSK9 example represents a paradigm or an isolated exception. We used the "Exome Array" to genotype >200,000 low-frequency and rare coding sequence variants across the genome in 56,538 individuals (42,208 European ancestry [EA] and 14,330 African ancestry [AA]) and tested these variants for association with LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. Although we did not identify new genes associated with LDL-C, we did identify four low-frequency (frequencies between 0.1% and 2%) variants (ANGPTL8 rs145464906 [c.361C>T; p.Gln121*], PAFAH1B2 rs186808413 [c.482C>T; p.Ser161Leu], COL18A1 rs114139997 [c.331G>A; p.Gly111Arg], and PCSK7 rs142953140 [c.1511G>A; p.Arg504His]) with large effects on HDL-C and/or triglycerides. None of these four variants was associated with risk for CHD, suggesting that examples of low-frequency coding variants with robust effects on both lipids and CHD will be limited.
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Triglicerídeos / Variação Genética / Doença das Coronárias / Frequência do Gene / HDL-Colesterol / LDL-Colesterol Idioma: En Ano de publicação: 2014 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Triglicerídeos / Variação Genética / Doença das Coronárias / Frequência do Gene / HDL-Colesterol / LDL-Colesterol Idioma: En Ano de publicação: 2014 Tipo de documento: Article