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Whole blood gene expression and atrial fibrillation: the Framingham Heart Study
Honghuang Lin1, Xiaoyan Yin2, Kathryn L Lunetta3
1Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America; National Heart Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts, United States of America.
Background:
Atrial fibrillation (AF) involves substantial electrophysiological, structural and contractile remodeling. We hypothesize that characterizing gene expression might uncover important pathways related to AF.
Methods And Results:
We performed genome-wide whole blood transcriptomic profiling (Affymetrix Human Exon 1.0 ST Array) of 2446 participants (mean age 66 ± 9 years, 55% women) from the Offspring cohort of Framingham Heart Study. The study included 177 participants with prevalent AF, 143 with incident AF during up to 7 years follow up, and 2126 participants with no AF. We identified seven genes statistically significantly up-regulated with prevalent AF. The most significant gene, PBX1 (P = 2.8 × 10(-7)), plays an important role in cardiovascular development. We integrated differential gene expression with gene-gene interaction information to identify several signaling pathways possibly involved in AF-related transcriptional regulation. We did not detect any statistically significant transcriptomic associations with incident AF.
Conclusion:
We examined associations of gene expression with AF in a large community-based cohort. Our study revealed several genes and signaling pathways that are potentially involved in AF-related transcriptional regulation.