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Genome sequencing unveils a regulatory landscape of platelet reactivity.
Keramati, Ali R; Chen, Ming-Huei; Rodriguez, Benjamin A T; Yanek, Lisa R; Bhan, Arunoday; Gaynor, Brady J; Ryan, Kathleen; Brody, Jennifer A; Zhong, Xue; Wei, Qiang; Kammers, Kai; Kanchan, Kanika; Iyer, Kruthika; Kowalski, Madeline H; Pitsillides, Achilleas N; Cupples, L Adrienne; Li, Bingshan; Schlaeger, Thorsten M; Shuldiner, Alan R; O'Connell, Jeffrey R; Ruczinski, Ingo; Mitchell, Braxton D; Faraday, Nauder; Taub, Margaret A; Becker, Lewis C; Lewis, Joshua P; Mathias, Rasika A; Johnson, Andrew D.
Afiliação
  • Keramati AR; Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Chen MH; GeneSTAR Research Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Rodriguez BAT; Division of Intramural Research, Population Sciences Branch, National Heart, Lung and Blood Institute, Bethesda, MD, USA.
  • Yanek LR; The Framingham Heart Study, Framingham, MA, USA.
  • Bhan A; Division of Intramural Research, Population Sciences Branch, National Heart, Lung and Blood Institute, Bethesda, MD, USA.
  • Gaynor BJ; The Framingham Heart Study, Framingham, MA, USA.
  • Ryan K; Valo Health, Boston, MA, USA.
  • Brody JA; GeneSTAR Research Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Zhong X; Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Wei Q; Boston Children's Hospital, Boston, MA, USA.
  • Kammers K; Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Baltimore, MD, USA.
  • Kanchan K; Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Iyer K; Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Baltimore, MD, USA.
  • Kowalski MH; Cardiovascular Health Research Unit, University of Washington School of Medicine, Seattle, WA, USA.
  • Pitsillides AN; Vanderbilt Genetics Institute, Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Cupples LA; Vanderbilt Genetics Institute, Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA.
  • Schlaeger TM; Biostatistics and Bioinformatics, Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Shuldiner AR; Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • O'Connell JR; Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Ruczinski I; Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA.
  • Mitchell BD; The Framingham Heart Study, Framingham, MA, USA.
  • Faraday N; Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.
  • Taub MA; The Framingham Heart Study, Framingham, MA, USA.
  • Becker LC; Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.
  • Lewis JP; Vanderbilt Genetics Institute, Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA.
  • Mathias RA; Boston Children's Hospital, Boston, MA, USA.
  • Johnson AD; Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Baltimore, MD, USA.
Nat Commun ; 12(1): 3626, 2021 06 15.
Article em En | MEDLINE | ID: mdl-34131117
ABSTRACT
Platelet aggregation at the site of atherosclerotic vascular injury is the underlying pathophysiology of myocardial infarction and stroke. To build upon prior GWAS, here we report on 16 loci identified through a whole genome sequencing (WGS) approach in 3,855 NHLBI Trans-Omics for Precision Medicine (TOPMed) participants deeply phenotyped for platelet aggregation. We identify the RGS18 locus, which encodes a myeloerythroid lineage-specific regulator of G-protein signaling that co-localizes with expression quantitative trait loci (eQTL) signatures for RGS18 expression in platelets. Gene-based approaches implicate the SVEP1 gene, a known contributor of coronary artery disease risk. Sentinel variants at RGS18 and PEAR1 are associated with thrombosis risk and increased gastrointestinal bleeding risk, respectively. Our WGS findings add to previously identified GWAS loci, provide insights regarding the mechanism(s) by which genetics may influence cardiovascular disease risk, and underscore the importance of rare variant and regulatory approaches to identifying loci contributing to complex phenotypes.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Plaquetas / Mapeamento Cromossômico / Sequenciamento Completo do Genoma Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Plaquetas / Mapeamento Cromossômico / Sequenciamento Completo do Genoma Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos