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Genome-wide association study of thoracic aortic aneurysm and dissection in the Million Veteran Program.
Klarin, Derek; Devineni, Poornima; Sendamarai, Anoop K; Angueira, Anthony R; Graham, Sarah E; Shen, Ying H; Levin, Michael G; Pirruccello, James P; Surakka, Ida; Karnam, Purushotham R; Roychowdhury, Tanmoy; Li, Yanming; Wang, Minxian; Aragam, Krishna G; Paruchuri, Kaavya; Zuber, Verena; Shakt, Gabrielle E; Tsao, Noah L; Judy, Renae L; Vy, Ha My T; Verma, Shefali S; Rader, Daniel J; Do, Ron; Bavaria, Joseph E; Nadkarni, Girish N; Ritchie, Marylyn D; Burgess, Stephen; Guo, Dong-Chuan; Ellinor, Patrick T; LeMaire, Scott A; Milewicz, Dianna M; Willer, Cristen J; Natarajan, Pradeep; Tsao, Philip S; Pyarajan, Saiju; Damrauer, Scott M.
Afiliación
  • Klarin D; Veterans Affairs (VA) Palo Alto Healthcare System, Palo Alto, CA, USA. dklarin@stanford.edu.
  • Devineni P; Department of Surgery, Stanford University School of Medicine, Palo Alto, CA, USA. dklarin@stanford.edu.
  • Sendamarai AK; Center for Data and Computational Sciences, VA Boston Healthcare System, Boston, MA, USA.
  • Angueira AR; Center for Data and Computational Sciences, VA Boston Healthcare System, Boston, MA, USA.
  • Graham SE; Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.
  • Shen YH; Department of Medicine, Harvard Medical School, Boston, MA, USA.
  • Levin MG; Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
  • Pirruccello JP; Department of Internal Medicine, Division of Cardiology, University of Michigan, Ann Arbor, MI, USA.
  • Surakka I; Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA.
  • Karnam PR; Department of Cardiovascular Surgery, Texas Heart Institute, Houston, TX, USA.
  • Roychowdhury T; Division of Cardiovascular Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
  • Li Y; Department of Medicine, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
  • Wang M; Division of Cardiology, University of California San Francisco, San Francisco, CA, USA.
  • Aragam KG; Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.
  • Paruchuri K; Department of Internal Medicine, Division of Cardiology, University of Michigan, Ann Arbor, MI, USA.
  • Zuber V; Center for Data and Computational Sciences, VA Boston Healthcare System, Boston, MA, USA.
  • Shakt GE; Department of Internal Medicine, Division of Cardiology, University of Michigan, Ann Arbor, MI, USA.
  • Tsao NL; Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
  • Judy RL; Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA.
  • Vy HMT; CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China.
  • Verma SS; University of Chinese Academy of Sciences, Beijing, China.
  • Rader DJ; Department of Medicine, Harvard Medical School, Boston, MA, USA.
  • Do R; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
  • Bavaria JE; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Nadkarni GN; Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Ritchie MD; Department of Medicine, Harvard Medical School, Boston, MA, USA.
  • Burgess S; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Guo DC; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
  • Ellinor PT; MRC Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
  • LeMaire SA; UK Dementia Research Institute at Imperial College, Imperial College London, London, UK.
  • Milewicz DM; Division of Cardiovascular Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
  • Willer CJ; Division of Cardiovascular Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
  • Natarajan P; Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
  • Tsao PS; Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Pyarajan S; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Damrauer SM; Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Nat Genet ; 55(7): 1106-1115, 2023 07.
Article en En | MEDLINE | ID: mdl-37308786
ABSTRACT
The current understanding of the genetic determinants of thoracic aortic aneurysms and dissections (TAAD) has largely been informed through studies of rare, Mendelian forms of disease. Here, we conducted a genome-wide association study (GWAS) of TAAD, testing ~25 million DNA sequence variants in 8,626 participants with and 453,043 participants without TAAD in the Million Veteran Program, with replication in an independent sample of 4,459 individuals with and 512,463 without TAAD from six cohorts. We identified 21 TAAD risk loci, 17 of which have not been previously reported. We leverage multiple downstream analytic methods to identify causal TAAD risk genes and cell types and provide human genetic evidence that TAAD is a non-atherosclerotic aortic disorder distinct from other forms of vascular disease. Our results demonstrate that the genetic architecture of TAAD mirrors that of other complex traits and that it is not solely inherited through protein-altering variants of large effect size.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Veteranos / Aneurisma de la Aorta Torácica / Disección Aórtica Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Veteranos / Aneurisma de la Aorta Torácica / Disección Aórtica Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos