title: Gene expression and genetic variation in human atria.
abstract: BACKGROUND
  The human left and right atria have different susceptibilities to develop atrial fibrillation (AF). However, the molecular events related to structural and functional changes that enhance AF susceptibility are still poorly understood.
  
  
  OBJECTIVE
  The purpose of this study was to characterize gene expression and genetic variation in human atria.
  
  
  METHODS
  We studied the gene expression profiles and genetic variations in 53 left atrial and 52 right atrial tissue samples collected from the Myocardial Applied Genomics Network (MAGNet) repository. The tissues were collected from heart failure patients undergoing transplantation and from unused organ donor hearts with normal ventricular function. Gene expression was profiled using the Affymetrix GeneChip Human Genome U133A Array. Genetic variation was profiled using the Affymetrix Genome-Wide Human SNP Array 6.0.
  
  
  RESULTS
  We found that 109 genes were differentially expressed between left and right atrial tissues. A total of 187 and 259 significant cis-associations between transcript levels and genetic variants were identified in left and right atrial tissues, respectively. We also found that a single nucleotide polymorphism at a known AF locus, rs3740293, was associated with the expression of MYOZ1 in both left and right atrial tissues.
  
  
  CONCLUSIONS
  We found a distinct transcriptional profile between the right and left atrium and extensive cis-associations between atrial transcripts and common genetic variants. Our results implicate MYOZ1 as the causative gene at the chromosome 10q22 locus for AF.
authors.affiliation: National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts; Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts. Electronic address: hhlin@bu.edu.
authors.forename: Honghuang
authors.initials: H
authors.lastname: Lin
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Dolmatova
authors.affiliation: Penn Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Morley
authors.affiliation: National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Lunetta
authors.affiliation: National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts; Cardiology Division, Department of Medicine, and Epidemiology Division, Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts.
authors.forename: David D
authors.initials: DD
authors.lastname: McManus
authors.affiliation: National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts; Section of Cardiovascular Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Jared W
authors.initials: JW
authors.lastname: Magnani
authors.affiliation: Penn Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Margulies
authors.affiliation: Penn Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.affiliation: Cardiovascular Institute, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Federica
authors.initials: F
authors.lastname: del Monte
authors.affiliation: National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts; Section of Cardiovascular Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts; Section of Preventive Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts; Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts.
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.affiliation: Penn Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Cappola
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts; Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts; Cardiac Arrhythmia Service, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Ellinor
mesh_terms: D001281:Atrial Fibrillation / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D004198:Disease Susceptibility; D015870:Gene Expression; D020869:Gene Expression Profiling; D056426:Genetic Loci; D014644:Genetic Variation; D005838:Genotype; D006325:Heart Atria; D006801:Humans; D009124:Muscle Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014158:Transcription, Genetic
chemical_list: D002352:Carrier Proteins; C419780:MYOZ1 protein, human; D009124:Muscle Proteins
keywords: AF; Atrial tissue; Expression quantitative trait loci; FDR; GWAS; Gene expression; Genetics; LA; MAGNet; Myocardial Applied Genomics Network; RA; SNP; atrial fibrillation; eQTL; expression quantitative trait loci; false discovery rate; genome-wide association studies; left atrium; right atrium; single nucleotide polymorphism