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


MeSH Major

  • Aortic Aneurysm, Thoracic
  • Chromosomes, Human, Pair 15
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Microfilament Proteins


  • 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.

publication date

  • October 2011



  • Review



  • eng

PubMed Central ID

  • PMC3244938

Digital Object Identifier (DOI)

  • 10.1038/ng.934

PubMed ID

  • 21909107

Additional Document Info

start page

  • 996

end page

  • 1000


  • 43


  • 10