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.