PT - JOURNAL ARTICLE AU - Courtney L. Kagan AU - Nicholas E Banovich AU - Bryan J Pavlovic AU - Kristen Patterson AU - Irene Gallego Romero AU - Jonathan K Pritchard AU - Yoav Gilad TI - Genetic Variation, Not Cell Type of Origin, Underlies Regulatory Differences in iPSCs AID - 10.1101/013888 DP - 2015 Jan 01 TA - bioRxiv PG - 013888 4099 - http://biorxiv.org/content/early/2015/01/19/013888.short 4100 - http://biorxiv.org/content/early/2015/01/19/013888.full AB - The advent of induced pluripotent stem cells (iPSCs)1 revolutionized Human Genetics by allowing us to generate pluripotent cells from easily accessible somatic tissues. This technology can have immense implications for regenerative medicine, but iPSCs also represent a paradigm shift in the study of complex human phenotypes, including gene regulation and disease2-5. Yet, an unresolved caveat of the iPSC model system is the extent to which reprogrammed iPSCs retain residual phenotypes from their precursor somatic cells. To directly address this issue, we used an effective study design to compare regulatory phenotypes between iPSCs derived from two types of commonly used somatic precursor cells. We show that the cell type of origin only minimally affects gene expression levels and DNA methylation in iPSCs. Instead, genetic variation is the main driver of regulatory differences between iPSCs of different donors.