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Chunk #0 — Introduction

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Common genetic variation drives molecular heterogeneity in human iPSCs.
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Induced pluripotent stem cells (iPSCs) are important model systems for human disease1. A major open question is whether iPSCs can be used to study the functions of genetic variants associated with complex traits and normal human phenotypic variation. Previous work has suggested that individual iPSC lines are highly heterogeneous2–5, although some of these differences may arise due to genetic background of the donor6,7. Nonetheless, high variability could make iPSCs unsuitable cellular models for genetic variants with small effects. Existing iPSC lines also frequently have limited genetic and phenotypic data of variable quality, or are derived from individuals with severe genetic disorders, limiting their utility for studying other phenotypes.