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Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors

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  • معلومة اضافية
    • Contributors:
      Stroke, HUNT All-In; Group, China Kadoorie Biobank Collaborative; Consortium, BioBank Japan Project; Group, ICAN Study; Group, CADISP; investigators, Genetics and Observational Subarachnoid Haemorrhage (GOSH) Study; (ISGC), International Stroke Genetics Consortium; Morel, Sandrine; Bijlenga, Philippe Alexandre Pierre; Bordeaux population health (BPH); Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM); Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE); Institut Pasteur de Lille; Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [CHU Lille] (CHRU Lille); ANR-11-INBS-0013,IFB (ex Renabi-IFB),Institut français de bioinformatique(2011); ANR-11-LABX-0009,DISTALZ,Développement de stratégies innovantes pour une approche transdisciplinaire de la maladie d'Alzheime(2011); ANR-16-IDEX-0007,NExT (I-SITE),NExT (I-SITE)(2016)
    • بيانات النشر:
      Springer Science and Business Media LLC, 2020.
    • الموضوع:
      2020
    • نبذة مختصرة :
      Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits.
    • File Description:
      application/pdf
    • ISSN:
      1546-1718
      1061-4036
    • الرقم المعرف:
      10.1038/s41588-020-00725-7
    • Rights:
      Springer TDM
    • الرقم المعرف:
      edsair.doi.dedup.....3c50306e2fae7b5e6d75460eabd64130