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GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes.
Franceschini, Nora; Giambartolomei, Claudia; de Vries, Paul S; Finan, Chris; Bis, Joshua C; Huntley, Rachael P; Lovering, Ruth C; Tajuddin, Salman M; Winkler, Thomas W; Graff, Misa; Kavousi, Maryam; Dale, Caroline; Smith, Albert V; Hofer, Edith; van Leeuwen, Elisabeth M; Nolte, Ilja M; Lu, Lingyi; Scholz, Markus; Sargurupremraj, Muralidharan; Pitkänen, Niina; Franzén, Oscar; Joshi, Peter K; Noordam, Raymond; Marioni, Riccardo E; Hwang, Shih-Jen; Musani, Solomon K; Schminke, Ulf; Palmas, Walter; Isaacs, Aaron; Correa, Adolfo; Zonderman, Alan B; Hofman, Albert; Teumer, Alexander; Cox, Amanda J; Uitterlinden, André G; Wong, Andrew; Smit, Andries J; Newman, Anne B; Britton, Annie; Ruusalepp, Arno; Sennblad, Bengt; Hedblad, Bo; Pasaniuc, Bogdan; Penninx, Brenda W; Langefeld, Carl D; Wassel, Christina L; Tzourio, Christophe; Fava, Cristiano; Baldassarre, Damiano; O'Leary, Daniel H.
Afiliação
  • Franceschini N; Department of Epidemiology, University of North Carolina, Chapel Hill, NC, 27516, USA.
  • Giambartolomei C; Department of Pathology and Laboratory Medicine, University of California (UCLA), Los Angeles, Los Angeles, CA, 90095, USA.
  • de Vries PS; 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, TX, 77030, USA.
  • Finan C; Institute of Cardiovascular Science, University College London, London, WC1 6BT, UK.
  • Bis JC; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, 98101, USA.
  • Huntley RP; Institute of Cardiovascular Science, University College London, London, WC1 6BT, UK.
  • Lovering RC; Institute of Cardiovascular Science, University College London, London, WC1 6BT, UK.
  • Tajuddin SM; Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, 20892, USA.
  • Winkler TW; Department of Genetic Epidemiology, University of Regensburg, Regensburg, 93053, Germany.
  • Graff M; Department of Epidemiology, University of North Carolina, Chapel Hill, NC, 27516, USA.
  • Kavousi M; Department of Epidemiology, Erasmus Medical Center, Rotterdam, 3015, The Netherlands.
  • Dale C; Institute of Health Informatics, University College London, London, WC1E 6BT, UK.
  • Smith AV; Icelandic Heart Association, Kopavogur, IS-201, Iceland.
  • Hofer E; University of Iceland, Reykjavik, 101, Iceland.
  • van Leeuwen EM; Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, 8036, Austria.
  • Nolte IM; Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, 8036, Austria.
  • Lu L; Department of Epidemiology, Erasmus Medical Center, Rotterdam, 3015, The Netherlands.
  • Scholz M; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, 3015, The Netherlands.
  • Sargurupremraj M; Department of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.
  • Pitkänen N; Institute for Medical Informatics, Statistics and Epidemiology, , University of Leipzig, Leipzig, 04107, Germany.
  • Franzén O; LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, 04107, Germany.
  • Joshi PK; Univ. Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, CHU Bordeaux, F-33000, Bordeaux, France.
  • Noordam R; Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, 20520, Finland.
  • Marioni RE; Department of Genetics and Genomic Sciences, The Icahn Institute for Genomics and Multiscale Biology Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Hwang SJ; Clinical Gene Networks AB, Stockholm, 104 62, Sweden.
  • Musani SK; Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH8 9AG, UK.
  • Schminke U; Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, 2300, RC, The Netherlands.
  • Palmas W; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
  • Isaacs A; Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
  • Correa A; Population Sciences Branch, Division of Intramural Research, NHLBI, NIH, Framingham, MA, 01702-5827, USA.
  • Zonderman AB; National Heart, Lung and Blood Institute's Intramural Research Program, Framingham Heart Study, Framingham, MA, 01702-5827, USA.
  • Hofman A; Department of Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
  • Teumer A; Department of Neurology, University Medicine Greifswald, Greifswald, 17475, Germany.
  • Cox AJ; Department of Medicine, Columbia University, New York, NY, 10032, USA.
  • Uitterlinden AG; Department of Epidemiology, Erasmus Medical Center, Rotterdam, 3015, The Netherlands.
  • Wong A; Department of Biochemistry, Maastricht Centre for Systems Biology (MaCSBio), CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, 6229, The Netherlands.
  • Smit AJ; Department of Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
  • Newman AB; Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, 20892, USA.
  • Britton A; Department of Epidemiology, Erasmus Medical Center, Rotterdam, 3015, The Netherlands.
  • Ruusalepp A; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.
  • Sennblad B; Institute for Community Medicine, University Medicine Greifswald, Greifswald, 17475, Germany.
  • Hedblad B; DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, 17475, Germany.
  • Pasaniuc B; Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, 25157, USA.
  • Penninx BW; Menzies Health Institute Queensland, Griffith University, Southport, QLD, 4222, Australia.
  • Langefeld CD; Department of Epidemiology, Erasmus Medical Center, Rotterdam, 3015, The Netherlands.
  • Wassel CL; Department of Internal Medicine, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, 3015, The Netherlands.
  • Tzourio C; MRC Unit for Lifelong Health and Ageing at UCL, London, WC1E 6BT, UK.
  • Fava C; Department of Medicine, University of Groningen, University Medical Center Groningen, Groningen, 2300, The Netherlands.
  • Baldassarre D; Department of Epidemiology, and School of Medicine, Division of Geriatric Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
  • O'Leary DH; Department of Epidemiology and Public Health, University College London, London, WC1E 6BT, UK.
Nat Commun ; 9(1): 5141, 2018 12 03.
Article em En | MEDLINE | ID: mdl-30510157
ABSTRACT
Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença das Coronárias / Predisposição Genética para Doença / Estudo de Associação Genômica Ampla / Placa Aterosclerótica / Espessura Intima-Media Carotídea Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
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PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença das Coronárias / Predisposição Genética para Doença / Estudo de Associação Genômica Ampla / Placa Aterosclerótica / Espessura Intima-Media Carotídea Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article