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Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification.
Kavousi, Maryam; Bos, Maxime M; Barnes, Hanna J; Lino Cardenas, Christian L; Wong, Doris; Lu, Haojie; Hodonsky, Chani J; Landsmeer, Lennart P L; Turner, Adam W; Kho, Minjung; Hasbani, Natalie R; de Vries, Paul S; Bowden, Donald W; Chopade, Sandesh; Deelen, Joris; Benavente, Ernest Diez; Guo, Xiuqing; Hofer, Edith; Hwang, Shih-Jen; Lutz, Sharon M; Lyytikäinen, Leo-Pekka; Slenders, Lotte; Smith, Albert V; Stanislawski, Maggie A; van Setten, Jessica; Wong, Quenna; Yanek, Lisa R; Becker, Diane M; Beekman, Marian; Budoff, Matthew J; Feitosa, Mary F; Finan, Chris; Hilliard, Austin T; Kardia, Sharon L R; Kovacic, Jason C; Kral, Brian G; Langefeld, Carl D; Launer, Lenore J; Malik, Shaista; Hoesein, Firdaus A A Mohamed; Mokry, Michal; Schmidt, Reinhold; Smith, Jennifer A; Taylor, Kent D; Terry, James G; van der Grond, Jeroen; van Meurs, Joyce; Vliegenthart, Rozemarijn; Xu, Jianzhao; Young, Kendra A.
Afiliación
  • Kavousi M; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. m.kavousi@erasmusmc.nl.
  • Bos MM; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
  • Barnes HJ; Cardiovascular Research Center, Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Lino Cardenas CL; Cardiovascular Research Center, Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Wong D; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA.
  • Lu H; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
  • Hodonsky CJ; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
  • Landsmeer LPL; Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
  • Turner AW; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
  • Kho M; Central Diagnostics Laboratory, Division Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
  • Hasbani NR; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
  • de Vries PS; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
  • Bowden DW; Graduate School of Data Science, Seoul National University, Seoul, Republic of Korea.
  • Chopade S; Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Center at Houston, Houston, TX, USA.
  • Deelen J; Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Center at Houston, Houston, TX, USA.
  • Benavente ED; Department of Biochemistry, Wake Forest University Health Sciences, Winston-Salem, NC, USA.
  • Guo X; Institute of Cardiovascular Science, Faculty of Population Health, University College London, London, UK.
  • Hofer E; University College London British Heart Foundation Research Accelerator Centre, London, UK.
  • Hwang SJ; Biomedical Data Sciences, Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
  • Lutz SM; Max Planck Institute for Biology of Aging, Cologne, Germany.
  • Lyytikäinen LP; Laboratory of Experimental Cardiology, Division of Heart and Lungs, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands.
  • Slenders L; The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation (formerly Los Angeles Biomedical Research Institute) at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Smith AV; Department of Neurology, Clinical Division of Neurogeriatrics, Medical University of Graz, Graz, Austria.
  • Stanislawski MA; Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.
  • van Setten J; Population Sciences, NHLBI/NIH, Framingham, MA, USA.
  • Wong Q; Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care, Boston, MA, USA.
  • Yanek LR; Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
  • Becker DM; Central Diagnostics Laboratory, Division Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
  • Beekman M; Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
  • Budoff MJ; Icelandic Heart Association, Kopavogur, Iceland.
  • Feitosa MF; Department of Biomedical Informatics, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
  • Finan C; Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands.
  • Hilliard AT; Department of Biostatistics, University of Washington, Seattle, WA, USA.
  • Kardia SLR; GeneSTAR Research Program, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Kovacic JC; GeneSTAR Research Program, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Kral BG; Biomedical Data Sciences, Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
  • Langefeld CD; The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation (formerly Los Angeles Biomedical Research Institute) at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Launer LJ; Department of Genetics, Division of Statistical Genomics, Washington University School of Medicine, St. Louis, MO, USA.
  • Malik S; Institute of Cardiovascular Science, Faculty of Population Health, University College London, London, UK.
  • Hoesein FAAM; University College London British Heart Foundation Research Accelerator Centre, London, UK.
  • Mokry M; Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands.
  • Schmidt R; VA Palo Alto Healthcare System, Palo Alto, CA, USA.
  • Smith JA; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
  • Taylor KD; Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia.
  • Terry JG; St Vincent's Clinical School, University of NSW, Sydney, New South Wales, Australia.
  • van der Grond J; The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
  • van Meurs J; GeneSTAR Research Program, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Vliegenthart R; Department of Biostatistical Sciences and Data Science, Wake Forest University Health Sciences, Winston-Salem, NC, USA.
  • Xu J; Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
  • Young KA; Susan Samueli Integrative Health Institute, Department of Medicine, University of California Irvine, Irvine, CA, USA.
Nat Genet ; 55(10): 1651-1664, 2023 Oct.
Article en En | MEDLINE | ID: mdl-37770635
Coronary artery calcification (CAC), a measure of subclinical atherosclerosis, predicts future symptomatic coronary artery disease (CAD). Identifying genetic risk factors for CAC may point to new therapeutic avenues for prevention. Currently, there are only four known risk loci for CAC identified from genome-wide association studies (GWAS) in the general population. Here we conducted the largest multi-ancestry GWAS meta-analysis of CAC to date, which comprised 26,909 individuals of European ancestry and 8,867 individuals of African ancestry. We identified 11 independent risk loci, of which eight were new for CAC and five had not been reported for CAD. These new CAC loci are related to bone mineralization, phosphate catabolism and hormone metabolic pathways. Several new loci harbor candidate causal genes supported by multiple lines of functional evidence and are regulators of smooth muscle cell-mediated calcification ex vivo and in vitro. Together, these findings help refine the genetic architecture of CAC and extend our understanding of the biological and potential druggable pathways underlying CAC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de la Arteria Coronaria / Aterosclerosis Tipo de estudio: Prognostic_studies / Risk_factors_studies / Systematic_reviews Límite: Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2023 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de la Arteria Coronaria / Aterosclerosis Tipo de estudio: Prognostic_studies / Risk_factors_studies / Systematic_reviews Límite: Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2023 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos