RT Journal Article SR Electronic T1 Common genetic variation drives molecular heterogeneity in human IPSCs JF bioRxiv FD Cold Spring Harbor Laboratory SP 055160 DO 10.1101/055160 A1 Helena Kilpinen A1 Angela Goncalves A1 Andreas Leha A1 Vackar Afzal A1 Sofie Ashford A1 Sendu Bala A1 Dalila Bensaddek A1 Francesco Paolo Casale A1 Oliver Culley A1 Petr Danacek A1 Adam Faulconbridge A1 Peter Harrison A1 Davis McCarthy A1 Shane A McCarthy A1 Ruta Meleckyte A1 Yasin Memari A1 Nathalie Moens A1 Filipa Soares A1 Ian Streeter A1 Chukwuma A Agu A1 Alex Alderton A1 Rachel Nelson A1 Sarah Harper A1 Minal Patel A1 Laura Clarke A1 Reena Halai A1 Christopher M Kirton A1 Anja Kolb-Kokocinski A1 Philip Beales A1 Ewan Birney A1 Davide Danovi A1 Angus I Lamond A1 Willem H Ouwehand A1 Ludovic Vallier A1 Fiona M Watt A1 Richard Durbin A1 Oliver Stegle A1 Daniel J Gaffney YR 2016 UL http://biorxiv.org/content/early/2016/05/25/055160.abstract AB 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 genomewide analyses we find that 5-25% of the variation in different iPSC phenotypes, including differentiation capacity and cellular morphology, arises from differences betweenindividuals. 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.