title: Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data.
abstract: BACKGROUND
  Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease.
  
  
  OBJECTIVE
  To identify common genetic variants associated with cardiac structure and function by conducting a meta-analysis of genome-wide association data in 5 population-based cohort studies (stage 1) with replication (stage 2) in 2 other community-based samples.
  
  
  METHODS
  Within each of 5 community-based cohorts comprising the EchoGen consortium (stage 1; n = 12 612 individuals of European ancestry; 55% women, aged 26-95 years; examinations between 1978-2008), we estimated the association between approximately 2.5 million single-nucleotide polymorphisms (SNPs; imputed to the HapMap CEU panel) and echocardiographic traits. In stage 2, SNPs significantly associated with traits in stage 1 were tested for association in 2 other cohorts (n = 4094 people of European ancestry). Using a prespecified P value threshold of 5 x 10(-7) to indicate genome-wide significance, we performed an inverse variance-weighted fixed-effects meta-analysis of genome-wide association data from each cohort.
  
  
  METHODS
  Echocardiographic traits: LV mass, internal dimensions, wall thickness, systolic dysfunction, aortic root, and left atrial size.
  
  
  RESULTS
  In stage 1, 16 genetic loci were associated with 5 echocardiographic traits: 1 each with LV internal dimensions and systolic dysfunction, 3 each with LV mass and wall thickness, and 8 with aortic root size. In stage 2, 5 loci replicated (6q22 locus associated with LV diastolic dimensions, explaining <1% of trait variance; 5q23, 12p12, 12q14, and 17p13 associated with aortic root size, explaining 1%-3% of trait variance).
  
  
  CONCLUSIONS
  We identified 5 genetic loci harboring common variants that were associated with variation in LV diastolic dimensions and aortic root size, but such findings explained a very small proportion of variance. Further studies are required to replicate these findings, identify the causal variants at or near these loci, characterize their functional significance, and determine whether they are related to overt cardiovascular disease.
authors: Framingham Heart Study, 73 Mt Wayte Ave, Ste 2, Framingham, MA 01702-5827, USA. vasan@bu.edu
authors: Ramachandran S
authors: RS
authors: Vasan
authors: Nicole L
authors: NL
authors: Glazer
authors: Janine F
authors: JF
authors: Felix
authors: Wolfgang
authors: W
authors: Lieb
authors: Philipp S
authors: PS
authors: Wild
authors: Stephan B
authors: SB
authors: Felix
authors: Norbert
authors: N
authors: Watzinger
authors: Martin G
authors: MG
authors: Larson
authors: Nicholas L
authors: NL
authors: Smith
authors: Abbas
authors: A
authors: Dehghan
authors: Anika
authors: A
authors: Grosshennig
authors: Arne
authors: A
authors: Schillert
authors: Alexander
authors: A
authors: Teumer
authors: Reinhold
authors: R
authors: Schmidt
authors: Sekar
authors: S
authors: Kathiresan
authors: Thomas
authors: T
authors: Lumley
authors: Yurii S
authors: YS
authors: Aulchenko
authors: Inke R
authors: IR
authors: König
authors: Tanja
authors: T
authors: Zeller
authors: Georg
authors: G
authors: Homuth
authors: Maksim
authors: M
authors: Struchalin
authors: Jayashri
authors: J
authors: Aragam
authors: Joshua C
authors: JC
authors: Bis
authors: Fernando
authors: F
authors: Rivadeneira
authors: Jeanette
authors: J
authors: Erdmann
authors: Renate B
authors: RB
authors: Schnabel
authors: Marcus
authors: M
authors: Dörr
authors: Robert
authors: R
authors: Zweiker
authors: Lars
authors: L
authors: Lind
authors: Richard J
authors: RJ
authors: Rodeheffer
authors: Karin Halina
authors: KH
authors: Greiser
authors: Daniel
authors: D
authors: Levy
authors: Talin
authors: T
authors: Haritunians
authors: Jaap W
authors: JW
authors: Deckers
authors: Jan
authors: J
authors: Stritzke
authors: Karl J
authors: KJ
authors: Lackner
authors: Uwe
authors: U
authors: Völker
authors: Erik
authors: E
authors: Ingelsson
authors: Iftikhar
authors: I
authors: Kullo
authors: Johannes
authors: J
authors: Haerting
authors: Christopher J
authors: CJ
authors: O'Donnell
authors: Susan R
authors: SR
authors: Heckbert
authors: Bruno H
authors: BH
authors: Stricker
authors: Andreas
authors: A
authors: Ziegler
authors: Thorsten
authors: T
authors: Reffelmann
authors: Margaret M
authors: MM
authors: Redfield
authors: Karl
authors: K
authors: Werdan
authors: Gary F
authors: GF
authors: Mitchell
authors: Kenneth
authors: K
authors: Rice
authors: Donna K
authors: DK
authors: Arnett
authors: Albert
authors: A
authors: Hofman
authors: John S
authors: JS
authors: Gottdiener
authors: Andre G
authors: AG
authors: Uitterlinden
authors: Thomas
authors: T
authors: Meitinger
authors: Maria
authors: M
authors: Blettner
authors: Nele
authors: N
authors: Friedrich
authors: Thomas J
authors: TJ
authors: Wang
authors: Bruce M
authors: BM
authors: Psaty
authors: Cornelia M
authors: CM
authors: van Duijn
authors: H-Erich
authors: HE
authors: Wichmann
authors: Thomas F
authors: TF
authors: Munzel
authors: Heyo K
authors: HK
authors: Kroemer
authors: Emelia J
authors: EJ
authors: Benjamin
authors: Jerome I
authors: JI
authors: Rotter
authors: Jacqueline C
authors: JC
authors: Witteman
authors: Heribert
authors: H
authors: Schunkert
authors: Helena
authors: H
authors: Schmidt
authors: Henry
authors: H
authors: Völzke
authors: Stefan
authors: S
authors: Blankenberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001011:Aorta / Q000033:anatomy & histology; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000235:genetics; D004452:Echocardiography; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006325:Heart Atria / Q000033:anatomy & histology; D006352:Heart Ventricles / Q000033:anatomy & histology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D018487:Ventricular Dysfunction, Left / Q000235:genetics; D016277:Ventricular Function, Left / Q000235:genetics*; D044465:White People