Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes

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Abstract

Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke subtypes. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy. © 2018 The Author(s)

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • Ludwig-Maximilian University of Munich
  • Indian Institute of Science
  • University of Bordeaux
  • University of Cambridge
  • Centre Hospitalier Universitaire de Bordeaux
  • RIKEN Center for Integrative Medical Sciences
  • Osaka University
  • Skåne University Hospital
  • University Hospital Munich
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Medicinsk genetik
  • Neurovetenskaper
Originalspråkengelska
Sidor (från-till)524-537
TidskriftNature Genetics
Volym50
Utgåva nummer4
Tidigt onlinedatum2018 mar 12
StatusPublished - 2018 apr
PublikationskategoriForskning
Peer review utfördJa