ArticleNature genetics2021
Identification of rare and common regulatory variants in pluripotent cells using population-scale transcriptomics.
Registry-linked trialAbstract read
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Article in Nature genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02450851 (Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network), which is not on this map. Cited by 41 papers, 4 of them syntheses that pooled it.
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41citing papers in PubMed, 4 pooled it
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network
Who cites it
41 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Trans-eQTL mapping prioritises USP18 as a negative regulator of interferon response at a lupus risk locus.Nature communications · 2025Pooled it
- Optimized summary-statistic-based single-cell eQTL meta-analysis.Scientific reports · 2025Pooled it
- Integration of GWAS, QTLs and keratinocyte functional assays reveals molecular mechanisms of atopic dermatitis.Nature communications · 2025Pooled it
- Genetic effects on the timing of parturition and links to fetal birth weight.Nature genetics · 2023Pooled it
- Reversible epiblast regionalization determines differentiation potential of human pluripotent stem cells.Nature biotechnology · 2026Article
- A genome-scale single-cell CRISPRi map of trans gene regulation across human pluripotent stem cell lines.Cell genomics · 2026Article
- High-resolution promoter interaction analysis implicates genes involved in the activation of Type 3 Innate Lymphoid Cells in autoimmune disease risk.bioRxiv : the preprint server for biology · 2026Article
- Article
- Harnessing iPSC technology for population-level human disease/traits modeling -where are we?Frontiers in cell and developmental biology · 2026Review
- Multiomic QTL mapping reveals phenotypic complexity of GWAS loci and prioritizes putative causal variants.Cell genomics · 2025Article
- iPSCs and iPSC-derived cells as a model of human genetic and epigenetic variation.Nature communications · 2025Article
- Cell type and dynamic state govern genetic regulation of gene expression in heterogeneous differentiating cultures.Cell genomics · 2024Article
- Homozygous variant in translocase of outer mitochondrial membrane 7 leads to metabolic reprogramming and microcephalic osteodysplastic dwarfism with moyamoya disease.EBioMedicine · 2024Article
- Individual variation in the emergence of anterior-to-posterior neural fates from human pluripotent stem cells.Stem cell reports · 2024Article
- RNA Sequencing in Disease Diagnosis.Annual review of genomics and human genetics · 2024Review
- PICALO: principal interaction component analysis for the identification of discrete technical, cell-type, and environmental factors that mediate eQTLs.Genome biology · 2024Article
- Splicing defects in rare diseases: transcriptomics and machine learning strategies towards genetic diagnosis.Briefings in bioinformatics · 2023Review
- Single-cell genomics meets human genetics.Nature reviews. Genetics · 2023Review
- Fine mapping spatiotemporal mechanisms of genetic variants underlying cardiac traits and disease.Nature communications · 2023Article
- Pitfalls and opportunities for applying latent variables in single-cell eQTL analyses.Genome biology · 2023Article
Corrections and comments
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Authors and funding
28 authors.
Marc Jan Bonder *European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, UK. bondermj@gmail.com.ORCID http://orcid.org/0000-0002-8431-3180
Craig Smail *Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA. csmail@stanford.edu.ORCID http://orcid.org/0000-0001-8045-6021
Michael J GloudemansDepartment of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-9924-9943
Laure FrésardDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
David JakuboskyBiomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA.
Matteo D'AntonioDepartment of Pediatrics and Rady Children's Hospital, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-5844-6433
Xin LiCAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Nicole M FerraroDepartment of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA.
Ivan Carcamo-OriveDivision of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-8823-4925
Bogdan MirautaEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, UK.
Daniel D SeatonEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, UK.ORCID http://orcid.org/0000-0002-5222-3893
Na CaiEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, UK.
Dara VakiliUCL Great Ormond Street Institute of Child Health, University College London, London, UK.ORCID http://orcid.org/0000-0001-8251-0589
Danilo HortaEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, UK.ORCID http://orcid.org/0000-0003-4832-2124
Chunli ZhaoStanford Center for Undiagnosed Diseases, Stanford University, Stanford, CA, USA.
Diane B ZastrowStanford Center for Undiagnosed Diseases, Stanford University, Stanford, CA, USA.
Devon E BonnerStanford Center for Undiagnosed Diseases, Stanford University, Stanford, CA, USA.
HipSci Consortium
iPSCORE consortium
Undiagnosed Diseases Network
PhLiPS consortium
Matthew T WheelerDivision of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-8721-3022
Helena KilpinenWellcome Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK.
Joshua W KnowlesDivision of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-1922-7240
Erin N SmithInstitute for Genomic Medicine, University of California, San Diego, La Jolla, CA, USA.
Kelly A FrazerDepartment of Pediatrics and Rady Children's Hospital, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-6060-8902
Stephen B MontgomeryDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA. smontgom@stanford.edu.ORCID http://orcid.org/0000-0002-5200-3903
Oliver StegleEuropean Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, UK. oliver.stegle@embl.de.ORCID http://orcid.org/0000-0002-8818-7193
Funding
POSTDOCTORAL TRAINING IN MEDICAL INFORMATION SCIENCEST15LM007033 · NLM · STANFORD UNIVERSITY · PI SYLVIA KATINA PLEVRITIS · 1985 to 2026
$25.5MStanford Islet Research CoreP30DK116074 · NIDDK · STANFORD UNIVERSITY · PI MANISHA DESAI · 2017 to 2026
$19.5MREGULATORY GENOMIC STUDIES IN A COHORT OF IPS CELL DERIVED CARDIOMYOCYTESU01HL107442 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI EVANS, SYLVIA M, FRAZER, KELLY A · 2011 to 2016
$9.8MIdentifying the gene networks of insulin resistance: the GENESIPS studyU01HL107388 · NHLBI · STANFORD UNIVERSITY · PI QUERTERMOUS, THOMAS, SCHADT, ERIC E · 2011 to 2015
$8.8MStanford Center for Undiagnosed DiseasesU01HG007708 · NHGRI · STANFORD UNIVERSITY · PI ASHLEY, EUAN A, BERNSTEIN, JONATHAN ADAM · 2014 to 2018
$8.0MWhat comes next? Engaging stakeholders in governance of participant data and relationships during the sunset of large genomic medicine research initiativesU01HG010218 · NHGRI · STANFORD UNIVERSITY · PI ASHLEY, EUAN A, BERNSTEIN, JONATHAN ADAM · 2018 to 2022
$6.3MOptimizing imputation for diverse populations in a distributed frameworkU01HG009080 · NHGRI · STANFORD UNIVERSITY · PI KENNY, EIMEAR ELIZABETH · 2016 to 2020
$5.2MFunctional Analysis of T2D Associated Non-coding SNPsU01DK105541 · NIDDK · LUDWIG INSTITUTE FOR CANCER RES LTD · PI FRAZER, KELLY A, REN, BING · 2015 to 2019
$4.6MMapping Molecular and Phenotypic Interactions in Alzheimers DiseaseR01AG066490 · NIA · STANFORD UNIVERSITY · PI MONTGOMERY, STEPHEN · 2020 to 2024
$3.6MDecoding the regulatory architecture of the human genome across cell types, individuals and diseaseU01HG009431 · NHGRI · STANFORD UNIVERSITY · PI PRITCHARD, JONATHAN K · 2017 to 2021
$3.5MFine-mapping and functional analysis of T1D-associated variantsDP3DK112155 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FRAZER, KELLY A, SANDER, MAIKE · 2016 to 2016
$3.3MCharacterization of novel insulin resistance genes by gene editing, high-throughput phenotyping and in vivo studiesR01DK120565 · NIDDK · STANFORD UNIVERSITY · PI KNOWLES, JOSHUA WILEY · 2019 to 2023
$3.2MMedical Research CouncilNHGRI NIH HHS R01 HG008150NHGRI NIH HHS U01 HG007708NHGRI NIH HHS U01 HG009080NHGRI NIH HHS U01 HG009431NHGRI NIH HHS U01 HG010218NHLBI NIH HHS R01 HL142015NHLBI NIH HHS U01 HL107388NHLBI NIH HHS U01 HL107442NIA NIH HHS R01 AG066490NIDDK NIH HHS DP3 DK112155NIDDK NIH HHS P30 DK116074NIDDK NIH HHS R01 DK106236NIDDK NIH HHS R01 DK107437NIDDK NIH HHS R01 DK116750NIDDK NIH HHS R01 DK120565NIDDK NIH HHS U01 DK105541NIH HHS S10 OD023452NLM NIH HHS T15 LM007033NLM NIH HHS T32 LM012409Wellcome TrustWellcome Trust WT090851Wellcome Trust WT098503
Abstract
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.
Indexed as
Genetic VariationQuantitative Trait LociBardet-Biedl SyndromeCalcium ChannelsCalcium Channels, N-TypeCell LineCerebellar AtaxiaDNA MethylationGene ExpressionHumansInduced Pluripotent Stem CellsPolymorphism, Single NucleotideProteinsRare DiseasesRegulatory Sequences, Nucleic AcidSequence Analysis, RNABbs2 protein, humanCACNA1A protein, humanCalcium ChannelsCalcium Channels, N-TypeProteins
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Registered trials
NCT02450851ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.