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Genome-wide association study of early ischaemic stroke risk in Brazilian individuals with sickle cell disease implicates ADAMTS2 and CDK18 and uncovers novel loci.
Earley, Eric Jay; Kelly, Shannon; Fang, Fang; Alencar, Cecília Salete; Rodrigues, Daniela de Oliveira Werneck; Soares Cruz, Dahra Teles; Flanagan, Jonathan M; Ware, Russell E; Zhang, Xu; Gordeuk, Victor; Gladwin, Mark; Zhang, Yingze; Nouraie, Mehdi; Nekhai, Sergei; Sabino, Ester; Custer, Brian; Dinardo, Carla; Page, Grier P.
Afiliação
  • Earley EJ; RTI International, Research Triangle Park, North Carolina, Durham, USA.
  • Kelly S; Benioff Children's Hospital, University of San Francisco, San Francisco, California, USA.
  • Fang F; Vitalant Research Institute, San Francisco, California, USA.
  • Alencar CS; RTI International, Research Triangle Park, North Carolina, Durham, USA.
  • Rodrigues DOW; Laboratório de Medicina Laboratorial LIM 03- HCFMUSP, São Paulo, Brazil.
  • Soares Cruz DT; Fundação Hemominas Juiz de Fora, Juiz de Fora, Brazil.
  • Flanagan JM; Department of Hematology, Fundação de Hematologia e Hemoterapia de Pernambuco, HEMOPE, Pernambuco, Brazil.
  • Ware RE; Division of Hematology and Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
  • Zhang X; Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
  • Gordeuk V; Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
  • Gladwin M; Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
  • Zhang Y; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  • Nouraie M; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  • Nekhai S; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  • Sabino E; Department of Medicine, Center for Sickle Cell Disease, Howard University, Washington, District of Columbia, USA.
  • Custer B; Instituto de Medicina Tropical, University of São Paulo, São Paulo, Brazil.
  • Dinardo C; Vitalant Research Institute, San Francisco, California, USA.
  • Page GP; Department of Laboratory Medicine, University of California, San Francisco, USA.
Br J Haematol ; 201(2): 343-352, 2023 04.
Article em En | MEDLINE | ID: mdl-36602125
Ischaemic stroke is a common complication of sickle cell disease (SCD) and without intervention can affect 11% of children with SCD before the age of 20. Within the Trans-Omics for Precision Medicine (TOPMed), a genome-wide association study (GWAS) of ischaemic stroke was performed on 1333 individuals with SCD from Brazil (178 cases, 1155 controls). Via a novel Cox proportional-hazards analysis, we searched for variants associated with ischaemic stroke occurring at younger ages. Variants at genome-wide significance (p < 5 × 10-8 ) include two near genes previously linked to non-SCD early-onset stroke (<65 years): ADAMTS2 (rs147625068, p = 3.70 × 10-9 ) and CDK18 (rs12144136, p = 2.38 × 10-9 ). Meta-analysis, which included the independent SCD cohorts Walk-PHaSST and PUSH, exhibited consistent association for variants rs1209987 near gene TBC1D32 (p = 3.36 × 10-10 ), rs188599171 near CUX1 (p = 5.89 × 10-11 ), rs77900855 near BTG1 (p = 4.66 × 10-8 ), and rs141674494 near VPS13C (1.68 × 10-9 ). Findings from this study support a multivariant model of early ischaemic stroke risk and possibly a shared genetic architecture between SCD individuals and non-SCD individuals younger than 65 years.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Isquemia Encefálica / Acidente Vascular Cerebral / AVC Isquêmico / Anemia Falciforme Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Adolescent / Adult / Child / Humans / Middle aged País/Região como assunto: America do sul / Brasil Idioma: En Revista: Br J Haematol Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Isquemia Encefálica / Acidente Vascular Cerebral / AVC Isquêmico / Anemia Falciforme Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Adolescent / Adult / Child / Humans / Middle aged País/Região como assunto: America do sul / Brasil Idioma: En Revista: Br J Haematol Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Reino Unido