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Heart Rhythm. 2014 Feb;11(2):266-71. doi: 10.1016/j.hrthm.2013.10.051. Epub 2013 Oct 28.

Gene expression and genetic variation in human atria.

Author information

1
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.
2
Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts.
3
Penn Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
4
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.
5
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.
6
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.
7
Cardiovascular Institute, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
8
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.
9
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.

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.

CONCLUSION:

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.

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

PMID:
24177373
PMCID:
PMC3946863
DOI:
10.1016/j.hrthm.2013.10.051
[Indexed for MEDLINE]
Free PMC Article
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