title: Genome-wide association study of cardiac structure and systolic function in African Americans: the Candidate Gene Association Resource (CARe) study.
abstract: BACKGROUND
  Using data from 4 community-based cohorts of African Americans, we tested the association between genome-wide markers (single-nucleotide polymorphisms) and cardiac phenotypes in the Candidate-gene Association Resource study.
  
  
  RESULTS
  Among 6765 African Americans, we related age, sex, height, and weight-adjusted residuals for 9 cardiac phenotypes (assessed by echocardiogram or magnetic resonance imaging) to 2.5 million single-nucleotide polymorphisms genotyped using Genome-wide Affymetrix Human SNP Array 6.0 (Affy6.0) and the remainder imputed. Within the cohort, genome-wide association analysis was conducted, followed by meta-analysis across cohorts using inverse variance weights (genome-wide significance threshold=4.0 ×10(-7)). Supplementary pathway analysis was performed. We attempted replication in 3 smaller cohorts of African ancestry and tested lookups in 1 consortium of European ancestry (EchoGEN). Across the 9 phenotypes, variants in 4 genetic loci reached genome-wide significance: rs4552931 in UBE2V2 (P=1.43×10(-7)) for left ventricular mass, rs7213314 in WIPI1 (P=1.68×10(-7)) for left ventricular internal diastolic diameter, rs1571099 in PPAPDC1A (P=2.57×10(-8)) for interventricular septal wall thickness, and rs9530176 in KLF5 (P=4.02×10(-7)) for ejection fraction. Associated variants were enriched in 3 signaling pathways involved in cardiac remodeling. None of the 4 loci replicated in cohorts of African ancestry was confirmed in lookups in EchoGEN.
  
  
  CONCLUSIONS
  In the largest genome-wide association study of cardiac structure and function to date in African Americans, we identified 4 genetic loci related to left ventricular mass, interventricular septal wall thickness, left ventricular internal diastolic diameter, and ejection fraction, which reached genome-wide significance. Replication results suggest that these loci may be unique to individuals of African ancestry. Additional large-scale studies are warranted for these complex phenotypes.
authors.affiliation: Department of Medicine, University of Mississippi Medical Center, 2500 North State St, Jackson, MS 39216, USA. efox@medicine.umsmed.edu
authors.forename: Ervin R
authors.initials: ER
authors.lastname: Fox
authors.forename: Solomon K
authors.initials: SK
authors.lastname: Musani
authors.forename: Maja
authors.initials: M
authors.lastname: Barbalic
authors.forename: Honghuang
authors.initials: H
authors.lastname: Lin
authors.forename: Bing
authors.initials: B
authors.lastname: Yu
authors.forename: Kofo O
authors.initials: KO
authors.lastname: Ogunyankin
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Smith
authors.forename: Abdullah
authors.initials: A
authors.lastname: Kutlar
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Glazer
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Post
authors.forename: Dina N
authors.initials: DN
authors.lastname: Paltoo
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Dries
authors.forename: Deborah N
authors.initials: DN
authors.lastname: Farlow
authors.forename: Christine W
authors.initials: CW
authors.lastname: Duarte
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Kardia
authors.forename: Kristin J
authors.initials: KJ
authors.lastname: Meyers
authors.forename: Yan V
authors.initials: YV
authors.lastname: Sun
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
authors.forename: Amit A
authors.initials: AA
authors.lastname: Patki
authors.forename: Jin
authors.initials: J
authors.lastname: Sha
authors.forename: Xiangqui
authors.initials: X
authors.lastname: Cui
authors.forename: Tandaw E
authors.initials: TE
authors.lastname: Samdarshi
authors.forename: Alan D
authors.initials: AD
authors.lastname: Penman
authors.forename: Kirsten
authors.initials: K
authors.lastname: Bibbins-Domingo
authors.forename: Petra
authors.initials: P
authors.lastname: Bůžková
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.forename: David A
authors.initials: DA
authors.lastname: Bluemke
authors.forename: Alanna C
authors.initials: AC
authors.lastname: Morrison
authors.forename: Gerardo
authors.initials: G
authors.lastname: Heiss
authors.forename: J Jeffrey
authors.initials: JJ
authors.lastname: Carr
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Mosley
authors.forename: Herman A
authors.initials: HA
authors.lastname: Taylor
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.forename: Susan R
authors.initials: SR
authors.lastname: Heckbert
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Cappola
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000368:Aged; D015331:Cohort Studies; D003971:Diastole; D004452:Echocardiography; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006321:Heart / Q000033:anatomy & histology / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D013599:Systole; D044465:White People / Q000235:genetics