title: Common genetic variation in the 3'-BCL11B gene desert is associated with carotid-femoral pulse wave velocity and excess cardiovascular disease risk: the AortaGen Consortium.
abstract: BACKGROUND
  Carotid-femoral pulse wave velocity (CFPWV) is a heritable measure of aortic stiffness that is strongly associated with increased risk for major cardiovascular disease events.
  
  
  RESULTS
  We conducted a meta-analysis of genome-wide association data in 9 community-based European ancestry cohorts consisting of 20 634 participants. Results were replicated in 2 additional European ancestry cohorts involving 5306 participants. Based on a preliminary analysis of 6 cohorts, we identified a locus on chromosome 14 in the 3'-BCL11B gene desert that is associated with CFPWV (rs7152623, minor allele frequency=0.42, β=-0.075±0.012 SD/allele, P=2.8×10(-10); replication β=-0.086±0.020 SD/allele, P=1.4×10(-6)). Combined results for rs7152623 from 11 cohorts gave β=-0.076±0.010 SD/allele, P=3.1×10(-15). The association persisted when adjusted for mean arterial pressure (β=-0.060±0.009 SD/allele, P=1.0×10(-11)). Results were consistent in younger (<55 years, 6 cohorts, n=13 914, β=-0.081±0.014 SD/allele, P=2.3×10(-9)) and older (9 cohorts, n=12 026, β=-0.061±0.014 SD/allele, P=9.4×10(-6)) participants. In separate meta-analyses, the locus was associated with increased risk for coronary artery disease (hazard ratio=1.05; confidence interval=1.02-1.08; P=0.0013) and heart failure (hazard ratio=1.10, CI=1.03-1.16, P=0.004).
  
  
  CONCLUSIONS
  Common genetic variation in a locus in the BCL11B gene desert that is thought to harbor 1 or more gene enhancers is associated with higher CFPWV and increased risk for cardiovascular disease. Elucidation of the role this novel locus plays in aortic stiffness may facilitate development of therapeutic interventions that limit aortic stiffening and related cardiovascular disease events.
authors: Cardiovascular Engineering Inc., 1 Edgewater Drive, Norwood, MA 02062, USA. GaryFMitchell@mindspring.com
authors: Gary F
authors: GF
authors: Mitchell
authors: Germaine C
authors: GC
authors: Verwoert
authors: Kirill V
authors: KV
authors: Tarasov
authors: Aaron
authors: A
authors: Isaacs
authors: Albert V
authors: AV
authors: Smith
authors: Yasmin
authors: Ernst R
authors: ER
authors: Rietzschel
authors: Toshiko
authors: T
authors: Tanaka
authors: Yongmei
authors: Y
authors: Liu
authors: Afshin
authors: A
authors: Parsa
authors: Samer S
authors: SS
authors: Najjar
authors: Kevin M
authors: KM
authors: O'Shaughnessy
authors: Sigurdur
authors: S
authors: Sigurdsson
authors: Marc L
authors: ML
authors: De Buyzere
authors: Martin G
authors: MG
authors: Larson
authors: Mark P S
authors: MP
authors: Sie
authors: Jeanette S
authors: JS
authors: Andrews
authors: Wendy S
authors: WS
authors: Post
authors: Francesco U S
authors: FU
authors: Mattace-Raso
authors: Carmel M
authors: CM
authors: McEniery
authors: Gudny
authors: G
authors: Eiriksdottir
authors: Patrick
authors: P
authors: Segers
authors: Ramachandran S
authors: RS
authors: Vasan
authors: Marie Josee E
authors: MJ
authors: van Rijn
authors: Timothy D
authors: TD
authors: Howard
authors: Patrick F
authors: PF
authors: McArdle
authors: Abbas
authors: A
authors: Dehghan
authors: Elizabeth S
authors: ES
authors: Jewell
authors: Stephen J
authors: SJ
authors: Newhouse
authors: Sofie
authors: S
authors: Bekaert
authors: Naomi M
authors: NM
authors: Hamburg
authors: Anne B
authors: AB
authors: Newman
authors: Albert
authors: A
authors: Hofman
authors: Angelo
authors: A
authors: Scuteri
authors: Dirk
authors: D
authors: De Bacquer
authors: Mohammad Arfan
authors: MA
authors: Ikram
authors: Bruce M
authors: BM
authors: Psaty
authors: Christian
authors: C
authors: Fuchsberger
authors: Matthias
authors: M
authors: Olden
authors: Louise V
authors: LV
authors: Wain
authors: Paul
authors: P
authors: Elliott
authors: Nicholas L
authors: NL
authors: Smith
authors: Janine F
authors: JF
authors: Felix
authors: Jeanette
authors: J
authors: Erdmann
authors: Joseph A
authors: JA
authors: Vita
authors: Kim
authors: K
authors: Sutton-Tyrrell
authors: Eric J G
authors: EJ
authors: Sijbrands
authors: Serena
authors: S
authors: Sanna
authors: Lenore J
authors: LJ
authors: Launer
authors: Tim
authors: T
authors: De Meyer
authors: Andrew D
authors: AD
authors: Johnson
authors: Anna F C
authors: AF
authors: Schut
authors: David M
authors: DM
authors: Herrington
authors: Fernando
authors: F
authors: Rivadeneira
authors: Manuela
authors: M
authors: Uda
authors: Ian B
authors: IB
authors: Wilkinson
authors: Thor
authors: T
authors: Aspelund
authors: Thierry C
authors: TC
authors: Gillebert
authors: Luc
authors: L
authors: Van Bortel
authors: Emelia J
authors: EJ
authors: Benjamin
authors: Ben A
authors: BA
authors: Oostra
authors: Jingzhong
authors: J
authors: Ding
authors: Quince
authors: Q
authors: Gibson
authors: André G
authors: AG
authors: Uitterlinden
authors: Gonçalo R
authors: GR
authors: Abecasis
authors: John R
authors: JR
authors: Cockcroft
authors: Vilmundur
authors: V
authors: Gudnason
authors: Guy G
authors: GG
authors: De Backer
authors: Luigi
authors: L
authors: Ferrucci
authors: Tamara B
authors: TB
authors: Harris
authors: Alan R
authors: AR
authors: Shuldiner
authors: Cornelia M
authors: CM
authors: van Duijn
authors: Daniel
authors: D
authors: Levy
authors: Edward G
authors: EG
authors: Lakatta
authors: Jacqueline C M
authors: JC
authors: Witteman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002318:Cardiovascular Diseases / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016016:Proportional Hazards Models; D012097:Repressor Proteins / Q000235:genetics*; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D059289:Vascular Stiffness / Q000502:physiology; D055815:Young Adult
chemical_list: C479740:BCL11B protein, human; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins