The transcriptional regulatory networks that maintain pluripotency are unique to stem cells. We next investigated how common genetic variants modulate these networks to produce iPSC-specific genetic effects on expression. We used chromatin state annotations from 127 reference epigenomes from the Roadmap Epigenomics Project27 to quantify the fold enrichment of iPSC-specific and nonspecific eQTL sets across 25 chromatin states (using matched null variants; Methods). iPSC-specific eQTLs were enriched in active enhancers and poised promoters in PSCs and PSC-derived cell types, while shared eQTLs were enriched for active promoters and transcribed regions in somatic tissues (Fig. 4c). iPSC-specific eQTLs were also enriched for binding sites of NANOG, POU5F1 (OCT4), and multiple other pluripotency factors9,28 (Fig. 4d; Extended Data Fig. 8). Our results suggest that common genetic differences between individuals may affect expression regulation during early stages of development.
