03200nas a2200805   4500000000100000000000100001008004100002260001500043653002000058653002700078653003100105653003100136653002200167653001300189653001100202653003500213653002200248653001400270653002000284653002800304653001800332100002000350700002100370700001700391700001700408700001600425700001800441700001500459700002100474700002700495700002100522700001700543700002300560700002200583700001900605700001900624700002200643700001900665700001700684700001900701700001800720700001500738700001700753700002000770700001800790700001800808700001700826700001600843700001900859700002000878700001700898700001600915700002600931700002500957700001800982700001601000700001801016700002001034700002301054700002001077700001801097700001901115700001801134700002201152245007501174300001201249490000801261520111101269022001402380       2017                            d  c2017-06-1510aCells, Cultured10aCellular Reprogramming10aDNA Copy Number Variations10aGene Expression Regulation10aGenetic Variation10aGenotype10aHumans10ainduced pluripotent stem cells10aOrgan Specificity10aPhenotype10aQuality Control10aQuantitative Trait Loci10aTranscriptome1 aHelena Kilpinen1 aAngela Goncalves1 aAndreas Leha1 aVackar Afzal1 aKaur Alasoo1 aSofie Ashford1 aSendu Bala1 aDalila Bensaddek1 aFrancesco Paolo Casale1 aOliver J. Culley1 aPetr Danecek1 aAdam Faulconbridge1 aPeter W. Harrison1 aAnnie Kathuria1 aDavis McCarthy1 aShane A. McCarthy1 aRuta Meleckyte1 aYasin Memari1 aNathalie Moens1 aFilipa Soares1 aAlice Mann1 aIan Streeter1 aChukwuma A. Agu1 aAlex Alderton1 aRachel Nelson1 aSarah Harper1 aMinal Patel1 aAlistair White1 aSharad R. Patel1 aLaura Clarke1 aReena Halai1 aChristopher M. Kirton1 aAnja Kolb-Kokocinski1 aPhilip Beales1 aEwan Birney1 aDavide Danovi1 aAngus I. Lamond1 aWillem H. Ouwehand1 aLudovic Vallier1 aFiona M. Watt1 aRichard Durbin1 aOliver Stegle1 aDaniel J. Gaffney00aCommon genetic variation drives molecular heterogeneity in human iPSCs  a370-3750 v5463 aTechnology utilizing human induced pluripotent stem cells (iPS cells) has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterization of many existing iPS cell lines limits their potential use for research and therapy. Here we describe the systematic generation, genotyping and phenotyping of 711 iPS cell lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative. Our study outlines the major sources of genetic and phenotypic variation in iPS cells and establishes their suitability as models of complex human traits and cancer. Through genome-wide profiling we find that 5-46% of the variation in different iPS cell phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. Additionally, we assess the phenotypic consequences of genomic copy-number alterations that are repeatedly observed in iPS cells. In addition, we present a comprehensive map of common regulatory variants affecting the transcriptome of human pluripotent cells.  a1476-4687