Helena Kilpinen, Angela Goncalves, Andreas Leha, Vackar Afzal, Sofie Ashford, Sendu Bala, Dalila Bensaddek, Francesco Paolo Casale, Oliver Culley, Petr Danacek, Adam Faulconbridge, Peter Harrison, Davis McCarthy, Shane A McCarthy, Ruta Meleckyte, Yasin Memari, Nathalie Moens, Filipa Soares, Ian Streeter, Chukwuma A Agu, Alex Alderton, Rachel Nelson, Sarah Harper, Minal Patel, Laura Clarke, Reena Halai, Christopher M Kirton, Anja Kolb-Kokocinski, Philip Beales, Ewan Birney, Davide Danovi, Angus I Lamond, Willem H Ouwehand, Ludovic Vallier, Fiona M Watt, Richard Durbin, Oliver Stegle, Daniel J Gaffney

bioRxiv doi:10.1101/055160

Abstract

Induced pluripotent stem cell (iPSC) technology has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterisation of many existing iPSC lines limits their potential use for research and therapy. Here, we describe the systematic generation, genotyping and phenotyping of 522 open access human iPSCs derived from 189 healthy male and female individuals as part of the Human Induced Pluripotent Stem Cells Initiative (HipSci: http://www.hipsci.org). Our study provides a comprehensive picture of the major sources of genetic and phenotypic variation in iPSCs and establishes their suitability for use in genetic studies of complex human traits and cancer. Using a combination of genome-wide analyses we find that 5-25% of the variation in different iPSC phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. We also assess the phenotypic effects of rare, genomic copy number mutations that are recurrently seen following iPSC reprogramming and present an initial map of common regulatory variants affecting the transcriptome of pluripotent cells in humans.