Identification of rare and common regulatory variants in pluripotent cells using population-scale transcriptomics. Nature genetics Bonder, M. J., Smail, C., Gloudemans, M. J., Fresard, L., Jakubosky, D., D'Antonio, M., Li, X., Ferraro, N. M., Carcamo-Orive, I., Mirauta, B., Seaton, D. D., Cai, N., Vakili, D., Horta, D., Zhao, C., Zastrow, D. B., Bonner, D. E., HipSci Consortium, iPSCORE consortium, Undiagnosed Diseases Network, PhLiPS consortium, Wheeler, M. T., Kilpinen, H., Knowles, J. W., Smith, E. N., Frazer, K. A., Montgomery, S. B., Stegle, O., Jan Bonder, M., Seaton, D., Jakubosky, D. A., Brown, C. D., Park, Y. 2021


Induced pluripotent stem cells (iPSCs) are an established cellular system to study the impact of genetic variants in derived cell types and developmental contexts. However, in their pluripotent state, the disease impact of genetic variants is less well known. Here, we integrate data from 1,367 human iPSC lines to comprehensively map common and rare regulatory variants in human pluripotent cells. Using this population-scale resource, we report hundreds of new colocalization events for human traits specific to iPSCs, and find increased power to identify rare regulatory variants compared with somatic tissues. Finally, we demonstrate how iPSCs enable the identification of causal genes for rare diseases.

View details for DOI 10.1038/s41588-021-00800-7

View details for PubMedID 33664507