Evidence map›Paper›PMID 41593234›Full record

ArticleNature genetics2026

Genetics and environment distinctively shape the human immune cell epigenome.

Wenliang Wang, Manoj Hariharan, Wubin Ding, Anna Bartlett, Cesar Barragan, Rosa Castanon, Ruoxuan Wang, Vince Rothenberg, Haili Song, Joseph R Nery and 35 more

Abstract read
In one paragraph

Article in Nature genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

45 authors.

Wenliang Wang *Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Manoj Hariharan *Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-1006-5372
Wubin Ding *Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-5355-7561
Anna BartlettGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-7059-4033
Cesar BarraganGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Rosa CastanonGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-1791-002X
Ruoxuan WangGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Vince RothenbergGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Haili SongGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Joseph R NeryGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-0153-5659
Andrew AldridgeDuke University School of Medicine, Bryan Research Building, Durham, NC, USA.
Jordan AltshulGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Mia KenworthyGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Hanqing LiuGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Wei TianGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Jingtian ZhouGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Qiurui ZengGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Huaming ChenGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-5289-7882
Bei WeiDepartment of Genetics, Stanford University, Stanford, CA, USA.
Irem B GündüzIntegrative Cellular Biology & Bioinformatics Lab, Saarland University, Saarbrücken, Germany.ORCID http://orcid.org/0000-0003-2641-0916
Todd NorellHealthspan, Resilience, and Performance, Florida Institute for Human and Machine Cognition, Pensacola, FL, USA.
Timothy J BroderickHealthspan, Resilience, and Performance, Florida Institute for Human and Machine Cognition, Pensacola, FL, USA.
Micah T McClainCenter for Infectious Disease Diagnostics and Innovation, Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA.
Lisa L SatterwhiteDepartment of Civil and Environmental Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA.ORCID http://orcid.org/0000-0002-0231-2353
Thomas W BurkeCenter for Infectious Disease Diagnostics and Innovation, Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA.ORCID http://orcid.org/0000-0003-0592-5822
Elizabeth A PetzoldCenter for Infectious Disease Diagnostics and Innovation, Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA.
Xiling ShenTerasaki Institute for Biomedical Innovation, Los Angeles, CA, USA.
Christopher W WoodsCenter for Infectious Disease Diagnostics and Innovation, Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA.
Vance G FowlerCenter for Infectious Disease Diagnostics and Innovation, Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA.
Felicia RuffinCenter for Infectious Disease Diagnostics and Innovation, Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA.ORCID http://orcid.org/0000-0003-2176-6462
Parinya PanuwetGangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Dana B BarrGangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Jennifer L BeareBattelle Memorial Institute, Columbus, OH, USA.
Anthony K SmithBattelle Memorial Institute, Columbus, OH, USA.
Rachel R SpurbeckBattelle Memorial Institute, Columbus, OH, USA.
Sindhu VangetiDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
Irene RamosDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.ORCID http://orcid.org/0000-0002-0223-0120
German NudelmanDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
Stuart C SealfonDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.ORCID http://orcid.org/0000-0001-5791-1217
Flora CastellinoU.S. Department of Health and Human Services, Administration for Strategic Preparedness and Response, Biomedical Advanced Research and Development Authority, Washington, DC, USA.
Anna Maria WalleyBarinthus Biotherapeutics, Germantown, MD, USA.
Thomas EvansBarinthus Biotherapeutics, Germantown, MD, USA.
Fabian MüllerIntegrative Cellular Biology & Bioinformatics Lab, Saarland University, Saarbrücken, Germany.ORCID http://orcid.org/0000-0001-5809-2321
William J GreenleafDepartment of Genetics, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-1409-3095
Joseph R EckerGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA. ecker@salk.edu.ORCID http://orcid.org/0000-0001-5799-5895

Funding

PRODUCTION CENTER FOR MAPPING REGULATORY REGIONS OF THE HUMAN GENOMEUM1HG009442 · NHGRI · STANFORD UNIVERSITY · PI SNYDER, MICHAEL P. · 2017 to 2021
$20.1M
Special EquipmentP50HG007735 · NHGRI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2014 to 2018
$15.2M
High-throughput systematic characterization of regulatory element functionUM1HG009436 · NHGRI · STANFORD UNIVERSITY · PI BASSIK, MICHAEL C, GREENLEAF, WILLIAM JAMES · 2017 to 2021
$5.4M
HLA Fine Mapping to Elucidate S. aureus SusceptibilityR01AI165671 · NIAID · DUKE UNIVERSITY · PI FOWLER, VANCE G., SCOTT, WILLIAM K · 2021 to 2025
$3.8M
UC San Diego Genetics Training ProgramT32GM145427 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BRUCE A HAMILTON · 2022 to 2026
$2.6M
NHGRI NIH HHS P50 HG007735NHGRI NIH HHS UM1 HG009436NHGRI NIH HHS UM1 HG009442NIAID NIH HHS R01 AI165671NIGMS NIH HHS T32 GM145427United States Department of Defense | Defense Advanced Research Projects Agency (DARPA) W911NF-19-2-0185U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) P50-HG007735U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) UM1-HG009436U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) UM1-HG009442
6 · The paper itself

Abstract

The epigenome of human immune cells is shaped by both genetics and environmental factors, yet the relative contributions of these influences remain incompletely characterized. Here we use single-nucleus methylation sequencing and assay for transposase-accessible chromatin using sequencing (ATAC-seq) to systematically explore how pathogen and chemical exposures, along with genetic variation, are associated with changes in the immune cell epigenome. Distinct exposure-associated differentially methylated regions (eDMRs) and differentially accessible regions were identified, and a significant correlation between these two modalities was observed. Additionally, genotype-associated DMRs (gDMRs) were detected, indicating that eDMRs are enriched in regulatory regions, whereas gDMRs are preferentially located within gene body marks. Disease-associated single-nucleotide polymorphisms were frequently colocalized with methylation quantitative trait loci, providing cell-type-specific insights into the genetic basis of diseases. These findings highlight the complex interplay between genetic and environmental factors in shaping the immune cell epigenome and advance understanding of immune cell regulation in health and disease.

Indexed as

Epigenesis, GeneticEpigenomeGene-Environment InteractionChromatinDNA MethylationHumansPolymorphism, Single NucleotideQuantitative Trait LociChromatin

Identifiers

PMID41593234
PMCPMC12900638

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.