Open AccessIdentification of rare and common regulatory variants in pluripotent cells using population-scale transcriptomics
Author(s) -
Marc Jan Bonder,
Craig Smail,
Michael J. Gloudemans,
Laure Frésard,
David Jakubosky,
Matteo D’Antonio,
Xin Li,
Nicole M. Ferraro,
Iván Cárcamo-Orive,
Bogdan Mirauta,
Daniel D Seaton,
Na Cai,
Dara Vakili,
Danilo Horta,
Chunli Zhao,
Diane B. Zastrow,
Devon Bonner,
Matthew T. Wheeler,
Helena Kilpinen,
Joshua W. Knowles,
Erin N. Smith,
Kelly A. Frazer,
Stephen B. Montgomery,
Oliver Stegle
Publication year - 2021
Publication title -
nature genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 18.861
H-Index - 573
eISSN - 1546-1718
pISSN - 1061-4036
DOI - 10.1038/s41588-021-00800-7
Subject(s) - induced pluripotent stem cell , biology , somatic cell , computational biology , identification (biology) , population , genetics , transcriptome , gene , gene expression , embryonic stem cell , botany , demography , sociology
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.