Dynamic genetic regulation of gene expression during cellular differentiation

The impact of genetic regulatory elements on gene expression can change during differentiation and across cell types and environments. We mapped expression quantitative trait loci (eQTLs) throughout differentiation to elucidate the dynamics of genetic effects and the associated cell type specific mechanisms. To do so, we generated high resolution time-series RNA-sequencing data, capturing differentiation from induced pluripotent stem cells to cardiomyocytes with 16 time points in 19 human cell lines. Genetic effects on gene regulation in these data show clear temporal structure. We identified hundreds of dynamic eQTLs that change significantly over time, with enrichment in enhancers of relevant cell types. We also found nonlinear dynamic eQTLs, which have effects only during intermediate stages of differentiation. These include a variant associated with body mass index, highlighting that transient genetic effects can contribute to disease. We obtained RNA-seq data for 19 Yoruba individuals at 16 time points each during the differentiation from iPSC to cardiomyocyte. There are a total of 297 samples.