Genome-wide Association Study Identifies a Susceptibility Locus for Thoracic Aortic Aneurysms and Aortic Dissections Spanning FBN1 at 15q21.1

Overview

Journal Nat Genet

Specialty Genetics

Date 2011 Sep 13

PMID 21909107

Citations 97

Authors

Scott A LeMaire

Merry-Lynn N McDonald

Dong-Chuan Guo

Ludivine Russell

Charles C Miller 3rd

Ralph J Johnson

Mir Reza Bekheirnia

Luis M Franco

Mary Nguyen

Reed E Pyeritz

Joseph E Bavaria

Richard Devereux

Cheryl Maslen

Kathryn W Holmes

Kim Eagle

Simon C Body

Christine Seidman

J G Seidman

Eric M Isselbacher

Molly Bray

Joseph S Coselli

Anthony L Estrera

Hazim J Safi

John W Belmont

Suzanne M Leal

Dianna M Milewicz

Affiliations

Soon will be listed here.

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.

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