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Whole-genome sequencing uncovers two loci for coronary artery calcification and identifies ARSE as a regulator of vascular calcification.
de Vries, Paul S; Conomos, Matthew P; Singh, Kuldeep; Nicholson, Christopher J; Jain, Deepti; Hasbani, Natalie R; Jiang, Wanlin; Lee, Sujin; Lino Cardenas, Christian L; Lutz, Sharon M; Wong, Doris; Guo, Xiuqing; Yao, Jie; Young, Erica P; Tcheandjieu, Catherine; Hilliard, Austin T; Bis, Joshua C; Bielak, Lawrence F; Brown, Michael R; Musharoff, Shaila; Clarke, Shoa L; Terry, James G; Palmer, Nicholette D; Yanek, Lisa R; Xu, Huichun; Heard-Costa, Nancy; Wessel, Jennifer; Selvaraj, Margaret Sunitha; Li, Rebecca H; Sun, Xiao; Turner, Adam W; Stilp, Adrienne M; Khan, Alyna; Newman, Anne B; Rasheed, Asif; Freedman, Barry I; Kral, Brian G; McHugh, Caitlin P; Hodonsky, Chani; Saleheen, Danish; Herrington, David M; Jacobs, David R; Nickerson, Deborah A; Boerwinkle, Eric; Wang, Fei Fei; Heiss, Gerardo; Jun, Goo; Kinney, Greg L; Sigurslid, Haakon H; Doddapaneni, HarshaVardhan.
  • 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, USA.
  • Conomos MP; Genetic Analysis Center, Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.
  • Singh K; Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Nicholson CJ; Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Jain D; Genetic Analysis Center, Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.
  • Hasbani NR; 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, USA.
  • Jiang W; Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Lee S; Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Lino Cardenas CL; Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Lutz SM; PRecisiOn Medicine Translational Research (PROMoTeR) Center, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
  • Wong D; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Guo X; Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, USA.
  • Yao J; The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Young EP; The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Tcheandjieu C; Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA.
  • Hilliard AT; VA Palo Alto Healthcare System, Palo Alto, CA, USA.
  • Bis JC; Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Bielak LF; VA Palo Alto Healthcare System, Palo Alto, CA, USA.
  • Brown MR; Palo Alto Veterans Institute for Research, Palo Alto, CA, USA.
  • Musharoff S; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
  • Clarke SL; School of Public Health, Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
  • Terry JG; 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, USA.
  • Palmer ND; VA Palo Alto Healthcare System, Palo Alto, CA, USA.
  • Yanek LR; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
  • Xu H; VA Palo Alto Healthcare System, Palo Alto, CA, USA.
  • Heard-Costa N; Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Wessel J; Department of Radiology, Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Selvaraj MS; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  • Li RH; Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Sun X; Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Turner AW; Boston University School of Medicine, Boston, MA, USA.
  • Stilp AM; Boston University and National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA, USA.
  • Khan A; Department of Epidemiology, Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA.
  • Newman AB; Diabetes Translational Research Center, Indiana University, Indianapolis, IN, USA.
  • Rasheed A; Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Freedman BI; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Kral BG; Department of Medicine, Harvard Medical School, Boston, MA, USA.
  • McHugh CP; Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Hodonsky C; School of Public Health and Tropical Medicine, Department of Epidemiology, Tulane University, New Orleans, LA, USA.
  • Saleheen D; College of Medicine, Department of Medicine, Division of Nephrology, University of Illinois Chicago, Chicago, IL, USA.
  • Herrington DM; Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, USA.
  • Jacobs DR; Genetic Analysis Center, Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.
  • Nickerson DA; Genetic Analysis Center, Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.
  • Boerwinkle E; Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
  • Wang FF; Center For Non-Communicable Diseases, Karachi, Pakistan.
  • Heiss G; Section on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  • Jun G; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Kinney GL; Genetic Analysis Center, Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.
  • Sigurslid HH; Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, USA.
  • Doddapaneni H; Center For Non-Communicable Diseases, Karachi, Pakistan.
Nat Cardiovasc Res ; 2(12): 1159-1172, 2023 Dec.
Article en En | MEDLINE | ID: mdl-38817323
ABSTRACT
Coronary artery calcification (CAC) is a measure of atherosclerosis and a well-established predictor of coronary artery disease (CAD) events. Here we describe a genome-wide association study (GWAS) of CAC in 22,400 participants from multiple ancestral groups. We confirmed associations with four known loci and identified two additional loci associated with CAC (ARSE and MMP16), with evidence of significant associations in replication analyses for both novel loci. Functional assays of ARSE and MMP16 in human vascular smooth muscle cells (VSMCs) demonstrate that ARSE is a promoter of VSMC calcification and VSMC phenotype switching from a contractile to a calcifying or osteogenic phenotype. Furthermore, we show that the association of variants near ARSE with reduced CAC is likely explained by reduced ARSE expression with the G allele of enhancer variant rs5982944. Our study highlights ARSE as an important contributor to atherosclerotic vascular calcification, and a potential drug target for vascular calcific disease.
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Texto completo: 1 Banco de datos: MEDLINE Idioma: En Año: 2023 Tipo del documento: Article
Texto completo
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PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Idioma: En Año: 2023 Tipo del documento: Article