ArticleNature genetics2023
Mapping the dynamic genetic regulatory architecture of HLA genes at single-cell resolution.
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Article in Nature genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32citing papers in PubMed
5.7field-weighted citation impact, top 3% of its field
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Who cites it
32 citing papers in PubMed, 38 citations in OpenAlex.
- Genotype-phenotype correlations in autoimmune and autoinflammatory diseases: An NGS-based immunogenetic cohort study.Immunogenetics · 2026Article
- Decoding Immune Regulation: From Genetic Variation to Mechanism Through Single-Cell Genomics.Immune network · 2026Review
- Evaluating the Utilities of Foundation Models in Single-Cell Data Analysis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- scHG: A supercell framework with high-order graph learning enables scalable multi-omics analysis.PLoS computational biology · 2026Article
- eQTL analysis: A bridge from genome to mechanism.Genes & diseases · 2026Review
- Early and late RNA eQTL are driven by different genetic mechanisms.Nature communications · 2026Article
- Exploring the shared genetic architecture between periodontitis and cardiovascular disease.BDJ open · 2026Article
- Integrative mendelian randomization approaches for therapeutic target prioritisation in immune-mediated diseases.Scientific reports · 2026Article
- Evolution of the tuberculin skin test reveals generalisable Mtb-reactive T cell metaclones.Nature communications · 2026Article
- Multi-Omics Identification of Key Immune Molecules in Gestational Diabetes Mellitus: FKBP5 and HLA-DQA1 as Candidate Biomarkers.International journal of general medicine · 2026Article
- Risk stratification for immune checkpoint inhibitor rechallenge after acute kidney injury: towards a precision medicine framework.Frontiers in immunology · 2026Review
- HLA-DQB1*03:01 strongly affects age of onset of type 1 narcolepsy independently of DQA1 and ethnicity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The interactions between HLA alleles and immune indicators were associated with the risk of rheumatoid arthritis.Clinical rheumatology · 2025Article
- Modeling heterogeneity in single-cell perturbation states enhances detection of response eQTLs.Nature genetics · 2025Article
- Quantifying HLA transcripts by genotype in chimeric mixtures at single-cell resolution.bioRxiv : the preprint server for biology · 2025Article
- Deciphering state-dependent immune features from multi-layer omics data at single-cell resolution.Nature genetics · 2025Article
- A haplotype-resolved view of human gene regulation.bioRxiv : the preprint server for biology · 2025Article
- Understanding rheumatic disease through continuous cell state analysis.Nature reviews. Rheumatology · 2025Review
- Transcriptome-wide analysis of differential expression in perturbation atlases.Nature genetics · 2025Article
- Cell type and dynamic state govern genetic regulation of gene expression in heterogeneous differentiating cultures.Cell genomics · 2024Article
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Authors and funding
28 authors at 20 institutions in 6 countries.
Joyce B KangCenter for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.
Amber Z ShenCenter for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.
Saisriram GurajalaCenter for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.
Aparna NathanCenter for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.ORCID 0000-0002-5975-2851
Laurie RumkerCenter for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.
Vitor R C AguiarProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-4137-9518
Cristian ValenciaCenter for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.
Kaitlyn A LagattutaCenter for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.
Fan ZhangCenter for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.ORCID 0000-0002-6102-2970
Anna Helena JonssonDivision of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-9558-2474
Seyhan YazarGarvan Institute of Medical Research, Sydney, New South Wales, Australia.
Jose Alquicira-HernandezGarvan Institute of Medical Research, Sydney, New South Wales, Australia.
Hamed KhaliliDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Ashwin N AnanthakrishnanDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Karthik JagadeeshHarvard T. H. Chan School of Public Health, Boston, MA, USA.ORCID 0000-0002-0957-812X
Kushal DeyHarvard T. H. Chan School of Public Health, Boston, MA, USA.ORCID 0000-0002-3520-2345
Accelerating Medicines Partnership Program: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Network
Mark J DalyPsychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
Ramnik J XavierKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Laura T DonlinHospital for Special Surgery, New York, NY, USA.
Jennifer H AnolikDepartment of Medicine, University of Rochester Medical Center, Rochester, NY, USA.
Joseph E PowellGarvan Institute of Medical Research, Sydney, New South Wales, Australia.ORCID 0000-0002-5070-4124
Deepak A RaoDivision of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-9672-7746
Michael B BrennerDivision of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-6202-8445
Maria Gutierrez-ArcelusProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0001-7898-7691
Yang LuoCenter for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.ORCID 0000-0001-7385-6166
Saori SakaueCenter for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.
Soumya RaychaudhuriCenter for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA. soumya@broadinstitute.org.ORCID 0000-0002-1901-8265
Broad Institute · USBrigham and Women's Hospital · USHospital for Special Surgery · USUniversity of Rochester Medical Center · USCedars-Sinai Medical Center · USHarvard University · USNorthwestern University · USGarvan Institute of Medical Research · AUNorthwell Health · USQueen Elizabeth Hospital Birmingham · GBQueen Mary University of London · GBUniversity of Pittsburgh · USColumbia University · USHumanitas University · ITMemorial Sloan Kettering Cancer Center · USNational Institutes of Health · USOklahoma Medical Research Foundation · USUniversity of Birmingham · GBUniversity of California San Diego · USUniversity of Rochester · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MMedical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0MPilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3MRole of fibroblastic stromal cells and notch signaling in tissue inflammation in RA and SLEP01AI148102 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI Nir Hacohen · 2021 to 2026
$17.3MTraining Program in Bioinformatics and Integrative GenomicsT32HG002295 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Peter J Park · 2001 to 2026
$15.8MMedical Scientist Training ProgramT32GM144273 · NIGMS · HARVARD MEDICAL SCHOOL · PI David Shumway Jones, Jacqueline A. Lees · 2022 to 2026
$14.7MMECHANISMS OF ARTHRITIC &DERMATOLOGY DISORDERST32AR007530 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI Michael B. Brenner, Ellen M Gravallese · 1986 to 2026
$10.4MJoint Biology Consortium Resource-based CenterP30AR070253 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI Peter A Nigrovic, Jeffrey Andrew Sparks · 2016 to 2026
$9.4MDiscovery and Functional Impact of Common and Rare Variants in RAR01AR063759 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI Soumya Raychaudhuri · 2013 to 2026
$5.4MIntegrative analysis of high dimensional tissue molecular data to define key biological systems in autoimmune diseases (SBC)UC2AR081023 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI Soumya Raychaudhuri · 2022 to 2026
$4.8MRA-SLE Molecular Deconstruction Leadership CenterUH2AR067677 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI BRENNER, MICHAEL B., RAYCHAUDHURI, SOUMYA · 2014 to 2020
$4.3MPredicting the impact of genetic variants, genes and pathways on human DiseaseU01HG012009 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI ALKES L PRICE, Soumya Raychaudhuri · 2021 to 2026
$4.2MMedical Research Council MR/M007669/1Medical Research Council MR/P021220/1NCI NIH HHS P30 CA008748NHGRI NIH HHS R56 HG013083NHGRI NIH HHS T32 HG002295NHGRI NIH HHS U01 HG012009NIAID NIH HHS F30 AI157385NIAID NIH HHS F30 AI172238NIAID NIH HHS P01 AI148102NIAMS NIH HHS K08 AR077037NIAMS NIH HHS P30 AR070253NIAMS NIH HHS R01 AR063759NIAMS NIH HHS T32 AR007530NIAMS NIH HHS UC2 AR081023NIAMS NIH HHS UH2 AR067677NIDDK NIH HHS P30 DK043351NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32 GM144273
Abstract
The human leukocyte antigen (HLA) locus plays a critical role in complex traits spanning autoimmune and infectious diseases, transplantation and cancer. While coding variation in HLA genes has been extensively documented, regulatory genetic variation modulating HLA expression levels has not been comprehensively investigated. Here we mapped expression quantitative trait loci (eQTLs) for classical HLA genes across 1,073 individuals and 1,131,414 single cells from three tissues. To mitigate technical confounding, we developed scHLApers, a pipeline to accurately quantify single-cell HLA expression using personalized reference genomes. We identified cell-type-specific cis-eQTLs for every classical HLA gene. Modeling eQTLs at single-cell resolution revealed that many eQTL effects are dynamic across cell states even within a cell type. HLA-DQ genes exhibit particularly cell-state-dependent effects within myeloid, B and T cells. For example, a T cell HLA-DQA1 eQTL ( rs3104371 ) is strongest in cytotoxic cells. Dynamic HLA regulation may underlie important interindividual variability in immune responses.
Indexed as
Gene Expression RegulationQuantitative Trait LociGenome-Wide Association StudyHumansPolymorphism, Single Nucleotide
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