The incidence of atrial fibrillation (AF) increases with age. Identification of genes differentially expressed by age and AF may improve our understanding of AF pathogenesis.
We aimed to determine whether there are age related differences in the expression of AF-associated genes in human left atria.
RNA sequence data from 314 left atrial appendages was processed and aligned using best practices. The expression of 24,002 left atrial genes was jointly modeled using sex, race, rhythm (in the age analysis) and age (in the rhythm analysis), and 25 expression surrogate variable analysis covariates using the limma-voom approach. Genes that showed both differential expression (DE) by age and by AF vs sinus rhythm at time of surgery were selected for analysis.
The median age of patients included in the analysis was 61 (IQR 53-69). The majority of patients were male (67%), white (84%), and in sinus rhythm at the time of surgery (55%). 599 genes were significantly (q ≤ 0.05) differentially expressed by age and 592 by rhythm. 68 genes were differentially expressed by both age and rhythm. Of those genes, only CDH2 (age FC 1.002 per year, q = 0.046; rhythm FC 1.081, q = 0.016) and MYBBP1A (age FC 1.002 per year, q = 0.012; rhythm FC 1.073, q = 0.010) displayed significant concordant age and rhythm effects.
After controlling for sex, race, and multiple testing in our dataset, we saw limited gene expression concordance between age and AF. This may reflect prior reported ventricularization of atrial gene expression in permanent AF that has been speculated to move toward a dedifferentiated fetal phenotype in response to stress. CDH2, which encodes N-cadherin, has been implicated in atrial remodeling and may contribute to the role of age in AF.
© 2021 Published by Elsevier Inc.