Genome-wide association study identifies a susceptibility locus for thoracic aortic aneurysms and aortic dissections spanning FBN1 at 15q21.1.
Publication/Presentation Date
9-11-2011
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.
Volume
43
Issue
10
First Page
996
Last Page
1000
ISSN
1546-1718
Published In/Presented At
LeMaire, S. A., McDonald, M. L., Guo, D. C., Russell, L., Miller, C. C., 3rd, Johnson, R. J., Bekheirnia, M. R., Franco, L. M., Nguyen, M., Pyeritz, R. E., Bavaria, J. E., Devereux, R., Maslen, C., Holmes, K. W., Eagle, K., Body, S. C., Seidman, C., Seidman, J. G., Isselbacher, E. M., Bray, M., … Milewicz, D. M. (2011). Genome-wide association study identifies a susceptibility locus for thoracic aortic aneurysms and aortic dissections spanning FBN1 at 15q21.1. Nature genetics, 43(10), 996–1000. https://doi.org/10.1038/ng.934
Disciplines
Medicine and Health Sciences
PubMedID
21909107
Department(s)
Department of Surgery
Document Type
Article