title: Genome-wide association study identifies a susceptibility locus for thoracic aortic aneurysms and aortic dissections spanning FBN1 at 15q21.1.
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.
authors: Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA.
authors: Scott A
authors: SA
authors: LeMaire
authors: Merry-Lynn N
authors: ML
authors: McDonald
authors: Dong-Chuan
authors: DC
authors: Guo
authors: Ludivine
authors: L
authors: Russell
authors: Charles C
authors: CC
authors: Miller
authors: Ralph J
authors: RJ
authors: Johnson
authors: Mir Reza
authors: MR
authors: Bekheirnia
authors: Luis M
authors: LM
authors: Franco
authors: Mary
authors: M
authors: Nguyen
authors: Reed E
authors: RE
authors: Pyeritz
authors: Joseph E
authors: JE
authors: Bavaria
authors: Richard
authors: R
authors: Devereux
authors: Cheryl
authors: C
authors: Maslen
authors: Kathryn W
authors: KW
authors: Holmes
authors: Kim
authors: K
authors: Eagle
authors: Simon C
authors: SC
authors: Body
authors: Christine
authors: C
authors: Seidman
authors: J G
authors: JG
authors: Seidman
authors: Eric M
authors: EM
authors: Isselbacher
authors: Molly
authors: M
authors: Bray
authors: Joseph S
authors: JS
authors: Coselli
authors: Anthony L
authors: AL
authors: Estrera
authors: Hazim J
authors: HJ
authors: Safi
authors: John W
authors: JW
authors: Belmont
authors: Suzanne M
authors: SM
authors: Leal
authors: Dianna M
authors: DM
authors: Milewicz
mesh_terms: D017545:Aortic Aneurysm, Thoracic / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D000071838:Fibrillin-1; D000071837:Fibrillins; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques; D006801:Humans; D015810:Linkage Disequilibrium; D008382:Marfan Syndrome / Q000235:genetics; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D054392:Adipokines
chemical_list: D004247:DNA; D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines