Genome-wide association study identifies a susceptibility locus for thoracic aortic aneurysms and aortic dissections spanning FBN1 at 15q21.1

Academic Article

Abstract

  • Although thoracic aortic aneurysms and dissections (TAAD) can be inherited as a single-gene disorder, the genetic predisposition in the majority of affected people is poorly understood. In a multistage genome-wide association study (GWAS), we compared 765 individuals who had sporadic TAAD (STAAD) with 874 controls and identified common SNPs at a 15q21.1 locus that were associated with STAAD, with odds ratios of 1.6-1.8 that achieved genome-wide significance. We followed up 107 SNPs associated with STAAD with P < 1 × 10 -5 in the region, in two separate STAAD cohorts. The associated SNPs fall into a large region of linkage disequilibrium encompassing FBN1, which encodes fibrillin-1. FBN1 mutations cause Marfan syndrome, whose major cardiovascular complication is TAAD. This study shows that common genetic variants at 15q21.1 that probably act via FBN1 are associated with STAAD, suggesting a common pathogenesis of aortic disease in Marfan syndrome and STAAD. © 2011 Nature America, Inc. All rights reserved.
  • Published In

  • Nature Genetics  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 1610868
  • Author List

  • Lemaire SA; McDonald MLN; Guo DC; Russell L; Miller CC; Johnson RJ; Bekheirnia MR; Franco LM; Nguyen M; Pyeritz RE
  • Start Page

  • 996
  • End Page

  • 1002
  • Volume

  • 43
  • Issue

  • 10