Identification of rare and common regulatory variants in pluripotent cells using population-scale transcriptomics

Nat Genet. 2021 Mar;53(3):313-321. doi: 10.1038/s41588-021-00800-7. Epub 2021 Mar 4.


Induced pluripotent stem cells (iPSCs) are an established cellular system to study the impact of genetic variants in derived cell types and developmental contexts. However, in their pluripotent state, the disease impact of genetic variants is less well known. Here, we integrate data from 1,367 human iPSC lines to comprehensively map common and rare regulatory variants in human pluripotent cells. Using this population-scale resource, we report hundreds of new colocalization events for human traits specific to iPSCs, and find increased power to identify rare regulatory variants compared with somatic tissues. Finally, we demonstrate how iPSCs enable the identification of causal genes for rare diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bardet-Biedl Syndrome / genetics
  • Calcium Channels / genetics
  • Cell Line
  • Cerebellar Ataxia / genetics
  • DNA Methylation
  • Gene Expression
  • Genetic Variation*
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / physiology*
  • Polymorphism, Single Nucleotide
  • Proteins / genetics
  • Quantitative Trait Loci*
  • Rare Diseases / genetics
  • Regulatory Sequences, Nucleic Acid
  • Sequence Analysis, RNA
  • Whole Genome Sequencing


  • Bbs2 protein, human
  • CACNA1A protein, human
  • Calcium Channels
  • Proteins