CARDIAC EPIGENETICS: THE BIOLOGY OF NON-CODING ENHANCERS IN HUMAN HEARTS

Abstract

Identifying genetic markers for heart failure is challenging, and requires prohibitively large cohort sizes in genome-wide association studies in order to meet genome-wide statistical significance. Chromatin quantitative trait loci, elucidated by direct epigenetic profiling of specific human tissues, may contribute towards prioritizing variants for disease-association. Here, I carried out a series of projects with colleagues to capture non-coding genetic variants by performing epigenetic profiling in 70 human hearts. This mapped a comprehensive catalogue of 47,321 human heart enhancers. To identify cardiac histone acetylation quantitative trait loci(haQTL), G-SCI test employed to call out 1,680 haQTL. RNA-seq from the same heart samples proved haQTL to have significant association to gene expression in cis and through long range interactions, identified by Hi-C experiments. Finally, 62 haQTL were identified by colocalisation of haQTL with heart-related GWAS datasets. Mechanistically, these may indeed be mediated through modification of enhancer H3K27-acetylation and their corresponding gene regulation.