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Protein-altering and regulatory genetic variants near GATA4 implicated in bicuspid aortic valve.
Yang, Bo; Zhou, Wei; Jiao, Jiao; Nielsen, Jonas B; Mathis, Michael R; Heydarpour, Mahyar; Lettre, Guillaume; Folkersen, Lasse; Prakash, Siddharth; Schurmann, Claudia; Fritsche, Lars; Farnum, Gregory A; Lin, Maoxuan; Othman, Mohammad; Hornsby, Whitney; Driscoll, Anisa; Levasseur, Alexandra; Thomas, Marc; Farhat, Linda; Dubé, Marie-Pierre; Isselbacher, Eric M; Franco-Cereceda, Anders; Guo, Dong-Chuan; Bottinger, Erwin P; Deeb, G Michael; Booher, Anna; Kheterpal, Sachin; Chen, Y Eugene; Kang, Hyun Min; Kitzman, Jacob; Cordell, Heather J; Keavney, Bernard D; Goodship, Judith A; Ganesh, Santhi K; Abecasis, Gonçalo; Eagle, Kim A; Boyle, Alan P; Loos, Ruth J F; Eriksson, Per; Tardif, Jean-Claude; Brummett, Chad M; Milewicz, Dianna M; Body, Simon C; Willer, Cristen J.
Afiliação
  • Yang B; Department of Cardiac Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Zhou W; Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Jiao J; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Nielsen JB; Department of Cardiac Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Mathis MR; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Heydarpour M; Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Lettre G; Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Folkersen L; Montreal Heart Institute, Montreal, Quebec, Canada HIT 1C8.
  • Prakash S; Department of Medicine, Université de Montréal, Montreal, Quebec, Canada QC H3T 1J4.
  • Schurmann C; Cardiovascular Medicine Unit, Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm SE-171 76, Sweden.
  • Fritsche L; Center for Biological Sequence Analysis, Technical University of Denmark, Copenhagen DK-2800, Denmark.
  • Farnum GA; Department of Internal Medicine, Division of Medical Genetics, University of Texas Health Science Center at Houston McGovern Medical School, Houston, Texas 77030, USA.
  • Lin M; The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
  • Othman M; Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Hornsby W; Norwegian University of Science and Technology, Trondheim 7491, Norway.
  • Driscoll A; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Levasseur A; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Thomas M; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan 48105, USA.
  • Farhat L; Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Dubé MP; Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Isselbacher EM; Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Franco-Cereceda A; Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Guo DC; Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Bottinger EP; Montreal Heart Institute, Montreal, Quebec, Canada HIT 1C8.
  • Deeb GM; Department of Medicine, Université de Montréal, Montreal, Quebec, Canada QC H3T 1J4.
  • Booher A; Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Kheterpal S; Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm SE-171 76, Sweden.
  • Chen YE; Department of Internal Medicine, Division of Medical Genetics, University of Texas Health Science Center at Houston McGovern Medical School, Houston, Texas 77030, USA.
  • Kang HM; The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
  • Kitzman J; Department of Cardiac Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Cordell HJ; Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Keavney BD; Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Goodship JA; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Ganesh SK; Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Abecasis G; Department of Cardiac Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Eagle KA; Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Boyle AP; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Loos RJF; Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Eriksson P; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Tardif JC; Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Brummett CM; Institute of Genetic Medicine, Newcastle University, Newcastle Upon Tyne NE1 3BZ, UK.
  • Milewicz DM; Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PL, UK.
  • Body SC; Manchester Heart Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL, UK.
  • Willer CJ; Institute of Genetic Medicine, Newcastle University, Newcastle Upon Tyne NE1 3BZ, UK.
Nat Commun ; 8: 15481, 2017 05 25.
Article em En | MEDLINE | ID: mdl-28541271
ABSTRACT
Bicuspid aortic valve (BAV) is a heritable congenital heart defect and an important risk factor for valvulopathy and aortopathy. Here we report a genome-wide association scan of 466 BAV cases and 4,660 age, sex and ethnicity-matched controls with replication in up to 1,326 cases and 8,103 controls. We identify association with a noncoding variant 151 kb from the gene encoding the cardiac-specific transcription factor, GATA4, and near-significance for p.Ser377Gly in GATA4. GATA4 was interrupted by CRISPR-Cas9 in induced pluripotent stem cells from healthy donors. The disruption of GATA4 significantly impaired the transition from endothelial cells into mesenchymal cells, a critical step in heart valve development.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Valva Aórtica / Variação Genética / Fator de Transcrição GATA4 / Doenças das Valvas Cardíacas Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Valva Aórtica / Variação Genética / Fator de Transcrição GATA4 / Doenças das Valvas Cardíacas Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Estados Unidos