Evidence map›Paper›PMID 41904542›Full record

ArticleGenome medicine2026

An atlas of genetic effects on the monocyte methylome across European and African populations.

Wanheng Zhang, Chuan Qiu, Xiao Zhang, Zichen Zhang, Kuan-Jui Su, Zhe Luo, Minghui Liu, Bingxin Zhao, Lang Wu, Qing Tian and 3 more

Abstract read
In one paragraph

Article in Genome medicine, 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

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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.

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

13 authors.

Wanheng Zhang *Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Chuan Qiu *Division of Biomedical Informatics and Genomics, Tulane Center for Biomedical Informatics and Genomics, Deming Department of Medicine, Tulane University, New Orleans, LA, 70112, USA.
Xiao ZhangDivision of Biomedical Informatics and Genomics, Tulane Center for Biomedical Informatics and Genomics, Deming Department of Medicine, Tulane University, New Orleans, LA, 70112, USA.
Zichen ZhangDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Kuan-Jui SuDivision of Biomedical Informatics and Genomics, Tulane Center for Biomedical Informatics and Genomics, Deming Department of Medicine, Tulane University, New Orleans, LA, 70112, USA.
Zhe LuoDivision of Biomedical Informatics and Genomics, Tulane Center for Biomedical Informatics and Genomics, Deming Department of Medicine, Tulane University, New Orleans, LA, 70112, USA.
Minghui LiuDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Bingxin ZhaoDepartment of Statistics and Data Science, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Lang WuCancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, 96813, USA.
Qing TianDivision of Biomedical Informatics and Genomics, Tulane Center for Biomedical Informatics and Genomics, Deming Department of Medicine, Tulane University, New Orleans, LA, 70112, USA.
Hui ShenDivision of Biomedical Informatics and Genomics, Tulane Center for Biomedical Informatics and Genomics, Deming Department of Medicine, Tulane University, New Orleans, LA, 70112, USA. hshen3@tulane.edu.
Chong WuDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. cwu18@mdanderson.org.
Hong-Wen DengDivision of Biomedical Informatics and Genomics, Tulane Center for Biomedical Informatics and Genomics, Deming Department of Medicine, Tulane University, New Orleans, LA, 70112, USA. hdeng2@tulane.edu.

Funding

Tulane COBRE in Cardiometabolic Diseases Clinical Research CoreP20GM109036 · NIGMS · TULANE UNIVERSITY OF LOUISIANA · PI Katherine Teresa Mills · 2016 to 2026
$25.3M
Trans-omics Integration of Multi-omics Studies for OsteoporosisU19AG055373 · NIA · TULANE UNIVERSITY OF LOUISIANA · PI Chuan Qiu · 2017 to 2026
$24.3M
Uncovering causal protein markers to improve prostate cancer etiology understanding and risk prediction in Africans and EuropeansR01CA263494 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI Chong Wu, Lang Wu · 2022 to 2026
$3.5M
Intensive Lifestyle Intervention, Metabolomics, and Risk of Frailty Fracture in Overweight or Obese Patients with Type 2 DiabetesR01AG068232 · NIA · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI JOHNSON, KAREN C, ZHAO, QI · 2021 to 2025
$3.1M
NCI NIH HHS R01 CA263494NIA NIH HHS R01 AG068232NIA NIH HHS U19 AG055373NIGMS NIH HHS P20 GM109036NIH HHS R01CA263494NIH HHS U19AG055373
6 · The paper itself

Abstract

backgroundGenetic regulation of DNA methylation in immune cells may mediate complex disease risk. However, current epigenomic studies are constrained by microarray CpG coverage, mixed-cell tissues, and limited representation of diverse ancestries. Thus, we generated a whole-genome, multi-ancestry atlas of genetic effects on the purified monocyte methylome.

methodsWe first performed whole-genome bisulfite sequencing (WGBS) of purified peripheral blood monocytes and whole-genome sequencing (WGS) from 160 African American (AA) and 298 European American (EA) participants, profiling around 25 million CpG sites. Next, we identified cis-methylation quantitative trait loci (meQTLs), estimated cis-heritability, and evaluated replication against large external meQTL resources. We further trained population-specific DNAm imputation models and applied them to methylome-wide association studies (MWAS) of 41 traits using genome-wide association study summary statistics from the Million Veteran Program. Type 2 diabetes signals were further evaluated using Mendelian randomization and Bayesian colocalization. We also conducted exploratory trans-meQTL mapping.

resultsWe identified 1,480,064 and 1,527,480 CpG sites with at least one cis-meQTL in AA and EA populations, respectively, including 543,869 shared sites and extensive population-specific regulation attributable to both allele-frequency differences and effect-size heterogeneity. Cis-meQTL effects replicated robustly in external datasets: effect sizes correlated strongly with prior studies (EA Pearson’s r = 0.76; 90.8% concordant directions; AA Pearson’s r = 0.71; 86.6% concordant directions). We built DNAm prediction models with cis-h2 > 0.01 for 2,677,714 CpG sites in AA and 1,976,046 CpG sites in EA, achieving mean cross-validated prediction R2 of 0.20 and 0.18. Across 41 traits, MWAS 23,650 significant methylation-phenotype associations (2,116 in AA and 21,534 in EA), of which ~ 98% were not interrogated by Illumina 450 K/EPIC arrays. For type 2 diabetes, MWAS identified 20 CpG sites in AA and 4,023 CpG sites in EA, with substantial support from Mendelian randomization and colocalization. Exploratory trans-meQTL mapping detected widespread long-range associations, with limited cross-study overlap but high directional concordance among shared signals.

conclusionsThis whole-genome, monocyte-resolved, multi-ancestry methylome atlas and accompanying imputation resource expand interpretable methylation variation beyond array-based studies and enable multi-ancestry integration of genetic, epigenetic, and genome-wide association study data to prioritize immune-cell regulatory mechanisms for complex disease.

Indexed as

DNA MethylationEpigenomeMonocytesAfrican PeopleBlack or African AmericanCpG IslandsDiabetes Mellitus, Type 2Epigenesis, GeneticGenome-Wide Association StudyHumansQuantitative Trait LociWhiteHeritabilityMeQTLMVPMWASWGBS

Identifiers

PMID41904542
PMCPMC13151332

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LicenceCC BY-NC-ND
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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.