Lateral Atrial Expression Patterns Provide Insights into Local Transcription Disequilibrium Contributing to Disease Susceptibility [Laterale atriale Expressionsmuster liefern Einblicke in lokale Transkriptionsungleichgewichte die zur Krankheitsanfälligkeit beitragen]

Isaacs A; Zeemering S; Winters J; Batlle M; Bidar E; Boukens B; Casadei B; Chua W; Crijns HJGM; Fabritz L; Guasch E; Hatem SN; Hermans B; Kaab S; Kawczynski M; Maesen B; Maessen J; Mont L; Sinner MF; Wakili R; Verheule S; Kirchhof P; Schotten U; Stoll M

Abstract

BACKGROUND:Transcriptional dysregulation, possibly affected by genetic variation, contributes to disease etiology. Due to dissimilarities in development, function, and remodeling during disease progression, transcriptional differences between the left atrium (LA) and right atrium (RA) may provide insight into diseases such as atrial fibrillation.METHODS:Lateral differences in atrial transcription were evaluated in CATCH ME (Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly) using a 2-stage discovery and replication design. The design took advantage of the availability of 32 paired samples, for which both LA and RA tissue were obtained, as a discovery cohort, and 98 LA and 69 RA unpaired samples utilized as a replication cohort.RESULTS:A total of 714 transcripts were identified and replicated as differentially expressed (DE) between LA and RA, as well as 98 exons in 55 genes. Approximately 50\% of DE transcripts were colocated with another frequently correlated DE transcript (PFDR