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Genome-wide association meta-analysis of spontaneous coronary artery dissection identifies risk variants and genes related to artery integrity and tissue-mediated coagulation.
Adlam, David; Berrandou, Takiy-Eddine; Georges, Adrien; Nelson, Christopher P; Giannoulatou, Eleni; Henry, Joséphine; Ma, Lijiang; Blencowe, Montgomery; Turley, Tamiel N; Yang, Min-Lee; Chopade, Sandesh; Finan, Chris; Braund, Peter S; Sadeg-Sayoud, Ines; Iismaa, Siiri E; Kosel, Matthew L; Zhou, Xiang; Hamby, Stephen E; Cheng, Jenny; Liu, Lu; Tarr, Ingrid; Muller, David W M; d'Escamard, Valentina; King, Annette; Brunham, Liam R; Baranowska-Clarke, Ania A; Debette, Stéphanie; Amouyel, Philippe; Olin, Jeffrey W; Patil, Snehal; Hesselson, Stephanie E; Junday, Keerat; Kanoni, Stavroula; Aragam, Krishna G; Butterworth, Adam S; Tweet, Marysia S; Gulati, Rajiv; Combaret, Nicolas; Kadian-Dodov, Daniella; Kalman, Jonathan M; Fatkin, Diane; Hingorani, Aroon D; Saw, Jacqueline; Webb, Tom R; Hayes, Sharonne N; Yang, Xia; Ganesh, Santhi K; Olson, Timothy M; Kovacic, Jason C; Graham, Robert M.
Afiliação
  • Adlam D; Department of Cardiovascular Sciences, Glenfield Hospital, Leicester, UK. da134@leicester.ac.uk.
  • Berrandou TE; NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK. da134@leicester.ac.uk.
  • Georges A; Université Paris Cité, Paris Cardiovascular Research Center, Inserm, Paris, France.
  • Nelson CP; Quantitative Genetics and Genomics, Aarhus University, Aarhus, Denmark.
  • Giannoulatou E; Université Paris Cité, Paris Cardiovascular Research Center, Inserm, Paris, France.
  • Henry J; Department of Cardiovascular Sciences, Glenfield Hospital, Leicester, UK.
  • Ma L; NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
  • Blencowe M; Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia.
  • Turley TN; School of Clinical Medicine, Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia.
  • Yang ML; Université Paris Cité, Paris Cardiovascular Research Center, Inserm, Paris, France.
  • Chopade S; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Finan C; Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Braund PS; Interdepartmental Program of Molecular, Cellular, and Integrative Physiology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Sadeg-Sayoud I; Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN, USA.
  • Iismaa SE; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
  • Kosel ML; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
  • Zhou X; Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI, USA.
  • Hamby SE; Institute for Cardiovascular Science, University College London, London, UK.
  • Cheng J; British Heart Foundation Research Accelerator, University College London, London, UK.
  • Liu L; Institute for Cardiovascular Science, University College London, London, UK.
  • Tarr I; British Heart Foundation Research Accelerator, University College London, London, UK.
  • Muller DWM; Department of Cardiovascular Sciences, Glenfield Hospital, Leicester, UK.
  • d'Escamard V; NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
  • King A; Université Paris Cité, Paris Cardiovascular Research Center, Inserm, Paris, France.
  • Brunham LR; Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia.
  • Baranowska-Clarke AA; School of Clinical Medicine, Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia.
  • Debette S; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
  • Amouyel P; Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
  • Olin JW; Department of Cardiovascular Sciences, Glenfield Hospital, Leicester, UK.
  • Patil S; NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
  • Hesselson SE; Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Junday K; Interdepartmental Program of Molecular, Cellular, and Integrative Physiology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Kanoni S; Université Paris Cité, Paris Cardiovascular Research Center, Inserm, Paris, France.
  • Aragam KG; Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia.
  • Butterworth AS; Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia.
  • Tweet MS; Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Gulati R; Centre for Heart Lung Innovation, Departments of Medicine and Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
  • Combaret N; Department of Cardiovascular Sciences, Glenfield Hospital, Leicester, UK.
  • Kadian-Dodov D; Department of Neurology, Bordeaux University Hospital, Inserm, Bordeaux, France.
  • Kalman JM; Université de Lille, Inserm, CHU Lille, Institut Pasteur de Lille, RID-AGE - Labex DISTALZ - Risk Factors and Molecular Determinants of Aging-Related Disease, Lille, France.
  • Fatkin D; Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Hingorani AD; Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
  • Saw J; Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia.
  • Webb TR; School of Clinical Medicine, Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia.
  • Hayes SN; Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia.
  • Yang X; School of Clinical Medicine, Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia.
  • Ganesh SK; William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • Olson TM; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
  • Kovacic JC; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Graham RM; Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nat Genet ; 55(6): 964-972, 2023 06.
Article em En | MEDLINE | ID: mdl-37248441
Spontaneous coronary artery dissection (SCAD) is an understudied cause of myocardial infarction primarily affecting women. It is not known to what extent SCAD is genetically distinct from other cardiovascular diseases, including atherosclerotic coronary artery disease (CAD). Here we present a genome-wide association meta-analysis (1,917 cases and 9,292 controls) identifying 16 risk loci for SCAD. Integrative functional annotations prioritized genes that are likely to be regulated in vascular smooth muscle cells and artery fibroblasts and implicated in extracellular matrix biology. One locus containing the tissue factor gene F3, which is involved in blood coagulation cascade initiation, appears to be specific for SCAD risk. Several associated variants have diametrically opposite associations with CAD, suggesting that shared biological processes contribute to both diseases, but through different mechanisms. We also infer a causal role for high blood pressure in SCAD. Our findings provide novel pathophysiological insights involving arterial integrity and tissue-mediated coagulation in SCAD and set the stage for future specific therapeutics and preventions.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças Vasculares / Doença da Artéria Coronariana / Infarto do Miocárdio Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Female / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças Vasculares / Doença da Artéria Coronariana / Infarto do Miocárdio Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Female / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article