Dynamic effects of genetic variation on gene expression revealed following hypoxic stress in cardiomyocytes.

摘要: One life-threatening outcome of cardiovascular disease is myocardial infarction, where cardiomyocytes are deprived oxygen. To study inter-individual differences in response to hypoxia, we established an vitro model induced pluripotent stem cell-derived from 15 individuals. We measured gene expression levels, chromatin accessibility, and methylation levels four culturing conditions that correspond normoxia, short- or long-term re-oxygenation. characterized thousands regulatory changes as the cells transition between conditions. Using available genotypes, identified 1,573 genes with a cis quantitative locus (eQTL) at least one condition, well 367 dynamic eQTLs, which classified eQTLs one, but not all A subset associated complex traits disease. Our data demonstrate how genetic effects on expression, likely relevant for disease, can be uncovered under stress.