期刊
NATURE GENETICS
卷 43, 期 10, 页码 996-U109出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.934
关键词
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资金
- US National Institutes of Health [P50-HL083794, R01-HL62594, UL1RR024148, UL1RR025758 (CTSA), K08-HL080085]
- Doris Duke Charitable Trust
- Vivian L. Smith Foundation
- TexGen Foundation
- Thoracic Surgery Foundation for Research and Education
- US Federal Government
- National Heart, Lung, and Blood Institute [N01-HV-68199]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
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 x 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.
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