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DNA methylation in lung cells is associated with asthma endotypes and genetic risk
Open accessAbstract
The epigenome provides a substrate through which environmental exposures can exert their effects on gene expression and disease risk, but the relative importance of epigenetic variation on human disease onset and progression is poorly characterized. Asthma is a heterogeneous disease of the airways, for which both onset and clinical course result from interactions between host genotype and environmental exposures, yet little is known about the molecular mechanisms for these interactions. We assessed genome-wide DNA methylation using the Infinium Human Methylation 450K Bead Chip and characterized the transcriptome by RNA sequencing in primary airway epithelial cells from 74 asthmatic and 41 nonasthmatic adults. Asthma status was based on doctor’s diagnosis and current medication use. Genotyping was performed using various Illumina platforms. Our study revealed a regulatory locus on chromosome 17q12-21 associated with asthma risk and epigenetic signatures of specific asthma endotypes and molecular networks. Overall, these data support a central role for DNA methylation in lung cells, which promotes distinct molecular pathways of asthma pathogenesis and modulates the effects of genetic variation on disease risk and clinical heterogeneity.
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“Lung cell type specific priors were obtained from a DE study of freshly isolated airway epithelial cells of asthma patients and healthy controls55.”
From scPower accelerates and optimizes the design of multi-sample single cell transcriptomic studies (2021) · cites this paper as [55]
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Cites
BEDTools: a flexible suite of utilities for comparing genomic features
Quinlan, A. R., & Hall, I. M. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq033 · Cited by 27,437
WGCNA: an R package for weighted correlation network analysis
Langfelder, P., & Horvath, S. (2008) · BMC Bioinformatics · doi:10.1186/1471-2105-9-559 · Cited by 27,252
An integrated encyclopedia of DNA elements in the human genome
The ENCODE Project Consortium (2012) · Nature · doi:10.1038/nature11247 · Cited by 18,072
Heinz, S., Benner, C., Spann, N., Bertolino, E., Lin, Y. C., Laslo, P., Cheng, J. X., Murre, C., Singh, H., & Glass, C. K. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.004 · Cited by 13,382
Smyth, G. K. (2004) · Statistical Applications in Genetics and Molecular Biology · doi:10.2202/1544-6115.1027 · Cited by 11,829
The Human Genome Browser at UCSC
Kent, W. J., Sugnet, C. W., Furey, T. S., Roskin, K. M., Pringle, T. H., Zahler, A. M., & Haussler, A. D. (2002) · Genome Research · doi:10.1101/gr.229102 · Cited by 10,400
A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping
Rao, S. S. P., Huntley, M. H., Durand, N. C., Stamenova, E. K., Bochkov, I. D., Robinson, J. T., Sanborn, A. L., Machol, I., Omer, A. D., Lander, E. S., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.021 · Cited by 9,212
Integrative analysis of 111 reference human epigenomes
Roadmap Epigenomics Consortium, Kundaje, A., Meuleman, W., Ernst, J., Bilenky, M., Yen, A., Heravi-Moussavi, A., Kheradpour, P., Zhang, Z., Wang, J., et al. (2015) · Nature · doi:10.1038/nature14248 · Cited by 6,368
O'Leary, N. A., Wright, M. W., Brister, J. R., Ciufo, S., Haddad, D., McVeigh, R., Rajput, B., Robbertse, B., Smith-White, B., Ako-Adjei, D., et al. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkv1189 · Cited by 6,357
A General Framework for Weighted Gene Co-Expression Network Analysis
Zhang, B., & Horvath, S. (2005) · Statistical Applications in Genetics and Molecular Biology · doi:10.2202/1544-6115.1128 · Cited by 5,684
The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans
The GTEx Consortium, Ardlie, K. G., Deluca, D. S., Segrè, A. V., Sullivan, T. J., Young, T. R., Gelfand, E. T., Trowbridge, C. A., Maller, J. B., Tukiainen, T., et al. (2015) · Science · doi:10.1126/science.1262110 · Cited by 5,062
Self-citationAryee, M. J., Jaffe, A. E., Bravo, H. C., Ladd‐Acosta, C., Feinberg, A. P., Hansen, K. D., & Irizarry, R. A. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu049 · Cited by 4,389
Histone H3K27ac separates active from poised enhancers and predicts developmental state
Creyghton, M. P., Cheng, A. W., Welstead, G. G., Kooistra, T., Carey, B. W., Steine, E. J., Hanna, J., Lodato, M. A., Frampton, G. M., Sharp, P. A., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016071107 · Cited by 4,302
Meta-analysis of the heritability of human traits based on fifty years of twin studies
Polderman, T. J. C., Benyamin, B., de Leeuw, C. A., Sullivan, P. F., van Bochoven, A., Visscher, P. M., & Posthuma, D. (2015) · Nature Genetics · doi:10.1038/ng.3285 · Cited by 2,467 · cited 1×
“The etiology of asthma is complex, with nearly equal contributions from genes and environment, reflected by heritability estimates of approximately 50% (3).”
BackgroundCombinatorial patterns of histone acetylations and methylations in the human genome
Wang, Z., Zang, C., Rosenfeld, J. A., Schones, D. E., Barski, A., Cuddapah, S., Cui, K., Roh, T.-Y., Peng, W., Zhang, M. Q., et al. (2008) · Nature Genetics · doi:10.1038/ng.154 · Cited by 2,331
Normalization of RNA-seq data using factor analysis of control genes or samples
Risso, D., Ngai, J., Speed, T. P., & Dudoit, S. (2014) · Nature Biotechnology · doi:10.1038/nbt.2931 · Cited by 2,052
A Large-Scale, Consortium-Based Genomewide Association Study of Asthma
Moffatt, M. F., Gut, I. G., Démenais, F., Strachan, D. P., Bouzigon, E., Heath, S. C., von Mutius, E., Farrall, M., Lathrop, M. G., & Cookson, W. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0906312 · Cited by 2,043
MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes
Li, Y., Willer, C. J., Ding, J., Scheet, P., & Abecasis, G. R. (2010) · Genetic Epidemiology · doi:10.1002/gepi.20533 · Cited by 1,843
Fast and accurate genotype imputation in genome-wide association studies through pre-phasing
Howie, B., Fuchsberger, C., Stephens, M., Marchini, J., & Abecasis, G. R. (2012) · Nature Genetics · doi:10.1038/ng.2354 · Cited by 1,737
Matrix eQTL: ultra fast eQTL analysis via large matrix operations
Shabalin, A. A. (2012) · Bioinformatics · doi:10.1093/bioinformatics/bts163 · Cited by 1,694
Gnirke, A., Melnikov, A., Maguire, J., Rogov, P., LeProust, E. M., Brockman, W., Fennell, T., Giannoukos, G., Fisher, S., Russ, C., et al. (2009) · Nature Biotechnology · doi:10.1038/nbt.1523 · Cited by 1,433 · cited 1×
“Promoter capture was performed as described previously (53) with the following changes: the in situ Hi-C library was hybridyzed to 81,735 biotinylated 120-bp custom RNA oligomers (Custom Array, Supplemental Table 7) targeting promoter regions.”
MethodTrait-associated SNPs are more likely to be eQTLs: annotation to enhance discovery from GWAS
Nicolae, D. L., Gamazon, E., Zhang, W., Duan, S., Dolan, M. E., & Cox, N. J. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000888 · Cited by 1,292
Self-citation(MCAAS), M. C. C. A. S., Ober, C., study, C. H. S. (. A. H., Genetics of Asthma in Latino Americans (GALA) Study, T. S. O. G.-E. A. A. I. L. A. (. A. T. S. O. A. A., (CAMP), C. A. M. P., (SAPPHIRE), S. O. A. P. A. P. I. B. R.-E., & Nicolae, D. L. (2011) · Nature Genetics · doi:10.1038/ng.888 · Cited by 846
Self-citationDNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines
Bell, J. T., Pai, A. A., Pickrell, J. K., Gaffney, D. J., Pique-Regi, R., Degner, J. F., Gilad, Y., & Pritchard, J. K. (2011) · Genome Biology · doi:10.1186/gb-2011-12-1-r10 · Cited by 838
Self-citationSWAN: Subset-quantile Within Array Normalization for Illumina Infinium HumanMethylation450 BeadChips
Maksimovic, J., Gordon, L., & Oshlack, A. (2012) · Genome Biology · doi:10.1186/gb-2012-13-6-r44 · Cited by 826
Evaluation of the Infinium Methylation 450K technology
Dedeurwaerder, S., Defrance, M., Calonne, E., Denis, H., Sotiriou, C., & Fuks, F. (2011) · Epigenomics · doi:10.2217/epi.11.105 · Cited by 569
On tests of the overall treatment effect in meta-analysis with normally distributed responses
Hartung, J., & Knapp, G. (2001) · Statistics in Medicine · doi:10.1002/sim.791 · Cited by 543
Rhinovirus Wheezing Illness and Genetic Risk of Childhood-Onset Asthma
Çalışkan, M., Bochkov, Y. A., Kreiner‐Møller, E., Bønnelykke, K., Stein, M. M., Du, G., Bisgaard, H. F., Jackson, D. J., Gern, J. E., Lemanske, R. F., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211592 · Cited by 538
Self-citationImpact of regulatory variation from RNA to protein
Battle, A., Khan, Z., Wang, S. H., Mitrano, A., Ford, M. J., Pritchard, J. K., & Gilad, Y. (2015) · Science · doi:10.1126/science.1260793 · Cited by 471
Self-citationMatrix eQTL: Ultra fast eQTL analysis via large matrix operationsPreprint
Shabalin, A. A. (2011) · arXiv (Cornell University) · doi:10.17615/g28n-r219 · Cited by 452
Exploring single-sample SNP and INDEL calling with whole-genomede novoassembly
Li, H. (2012) · Bioinformatics · doi:10.1093/bioinformatics/bts280 · Cited by 398
Cigarette smoking and DNA methylation
Lee, K. W. K., & Pausová, Z. (2013) · Frontiers in Genetics · doi:10.3389/fgene.2013.00132 · Cited by 384
Prevalence of asthma‐like symptoms in young children
Bisgaard, H., & Szefler, S. J. (2007) · Pediatric Pulmonology · doi:10.1002/ppul.20644 · Cited by 304
Banovich, N. E., Lan, X., McVicker, G., van de Geijn, B., Degner, J. F., Blischak, J., Roux, J., Pritchard, J. K., & Gilad, Y. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004663 · Cited by 292
Self-citationA Statistical Framework for Joint eQTL Analysis in Multiple Tissues
Flutre, T., Wen, X., Pritchard, J. K., & Stephens, M. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003486 · Cited by 259
An epigenome-wide association study of total serum immunoglobulin E concentration
Liang, L., Willis-Owen, S. A. G., Laprise, C., Wong, K. C. C., Davies, G. A., Hudson, T. J., Binia, A., Hopkin, J. M., Yang, I. V., Grundberg, E., et al. (2015) · Nature · doi:10.1038/nature14125 · Cited by 213
Human diseases through the lens of network biology
Furlong, L. I. (2012) · Trends in Genetics · doi:10.1016/j.tig.2012.11.004 · Cited by 196
Gene–environment interactions in human disease: nuisance or opportunity?
Ober, C., & Vercelli, D. (2011) · Trends in Genetics · doi:10.1016/j.tig.2010.12.004 · Cited by 188
Self-citationMendelian Randomization for Strengthening Causal Inference in Observational Studies
Smith, G. D. (2010) · Perspectives on Psychological Science · doi:10.1177/1745691610383505 · Cited by 186
Liver and Adipose Expression Associated SNPs Are Enriched for Association to Type 2 Diabetes
Zhong, H., Beaulaurier, J., Lum, P. Y., Molony, C. M., Yang, X., MacNeil, D. J., Weingarth, D. T., Zhang, B., Greenawalt, D. M., Dobrin, R., et al. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000932 · Cited by 165
Gamazon, E. R., Badner, J. A., Cheng, L., Zhang, C., Zhang, D., Cox, N. J., Gershon, E. S., Kelsoe, J. R., Greenwood, T. A., Nievergelt, C. M., et al. (2012) · Molecular Psychiatry · doi:10.1038/mp.2011.174 · Cited by 158
Zheng, S., De, B. P., Choudhary, S., Comhair, S. A. A., Goggans, T., Slee, R., Williams, B. R. G., Pilewski, J., Haque, S. J., & Erzurum, S. C. (2003) · Immunity · doi:10.1016/s1074-7613(03)00114-6 · Cited by 125
Leveraging gene-environment interactions and endotypes for asthma gene discovery
Bønnelykke, K., & Ober, C. (2016) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2016.01.006 · Cited by 113
Self-citationGenome-Wide Methylation Study Identifies an IL-13–induced Epigenetic Signature in Asthmatic Airways
Nicodemus‐Johnson, J., Naughton, K. A., Sudi, J., Hogarth, K. D., Naureckas, E. T., Nicolae, D. L., Sperling, A. I., Solway, J., White, S. R., & Ober, C. (2015) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201506-1243oc · Cited by 111
Self-citationEpigenetics, Asthma, and Allergic Diseases: A Review of the Latest Advancements
Lovinsky‐Desir, S., & Miller, R. L. (2012) · Current Allergy and Asthma Reports · doi:10.1007/s11882-012-0257-4 · Cited by 110
Murphy, A., Chu, J., Xu, M., Carey, V. J., Lazarus, R. M., Liu, A., Szefler, S. J., Strunk, R. C., DeMuth, K. A., Castro, M., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq392 · Cited by 107
Li, X., Hastie, A. T., Hawkins, G. A., Moore, W. C., Ampleford, E. J., Milošević, J., Li, H., Busse, W. W., ERZURUM, S. C., Kaminski, N., et al. (2015) · Allergy · doi:10.1111/all.12683 · Cited by 96
The role of epigenetics in the developmental origins of allergic disease
North, M. L., & Ellis, A. K. (2011) · Annals of Allergy Asthma & Immunology · doi:10.1016/j.anai.2011.02.008 · Cited by 90
Zhang, X., Johnson, A. D., Hendricks, A. E., Hwang, S., Tanrıverdi, K., Ganesh, S. K., Smith, N. L., Peyser, P. A., Freedman, J. E., & O’Donnell, C. J. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt461 · Cited by 57
Tandon, A., Patterson, N. J., & Reich, D. (2010) · Genetic Epidemiology · doi:10.1002/gepi.20550 · Cited by 56
Maternal asthma and microRNA regulation of soluble HLA-G in the airway
Nicodemus‐Johnson, J., Laxman, B., Stern, R. K., Sudi, J., Tierney, C. N., Norwick, L. M., Hogarth, D. K., McConville, J. F., Naureckas, E. T., Sperling, A. I., et al. (2013) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2013.01.037 · Cited by 50
Self-citationImmunomodulatory Role of Vascular Endothelial Growth Factor and Angiopoietin-1 in Airway Remodeling
Makinde, T. O., Murphy, R., & Agrawal, D. K. (2006) · Current Molecular Medicine · doi:10.2174/156652406779010795 · Cited by 46
Airway molecular endotypes of asthma
Wesolowska‐Andersen, A., & Seibold, M. A. (2015) · Current Opinion in Allergy and Clinical Immunology · doi:10.1097/aci.0000000000000148 · Cited by 35
The Role of Transforming Growth Factor-β1 in Airway Inflammation of Childhood Asthma
Gagliardo, R. P., Chanez, P., Gjomarkaj, M., Grutta, S. L., Bonanno, A., Montalbano, A. M., Sano, C. D., Albano, G. D., Gras, D., Anzalone, G., et al. (2013) · International Journal of Immunopathology and Pharmacology · doi:10.1177/039463201302600316 · Cited by 33
Role of Selectins in the Intestinal Epithelial Migration of Eosinophils
Michail, S. K., Mezoff, E. A., & Abernathy, F. (2005) · Pediatric Research · doi:10.1203/01.pdr.0000180572.65751.f4 · Cited by 20
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Metadata
- Authors
- Nicodemus-Johnson, J., Myers, R. A., Sakabe, N. J., Sobreira, D. R., Hogarth, D. K., Naureckas, E. T., Sperling, A. I., Solway, J., White, S. R., Nobrega, M. A., Nicolae, D. L., Gilad, Y., & Ober, C.
- Affiliations
- Department of Human Genetics,
- Department of Medicine, and
- University of Chicago (US)
- Corresponding author
- Ober, Carole
- ORCID
- Venue
- JCI Insight
- Published
- 2016-12-08
- Volume
- 1
- Issue
- 20
- Pages
- e90151-e90151
- ISSN
- 2379-3708 (ISSN-L)
- PMC
- PMC5139904
- OpenAlex
- W2560541504
- Cited by
- 180
- References
- 55
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 23 · 2023: 13 · 2022: 18 · 2021: 29 · 2020: 28 · 2019: 23 · 2018: 18 · 2017: 2
- FWCI
- 11.54
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- JCI Insight (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- AstraZeneca
- University of Chicago
- Cytokinetics
- National Institutes of Health (U01 AI106683)
- National Heart, Lung, and Blood Institute (P01HL070831, T32HL007605)
- National Institute of Allergy and Infectious Diseases (AI106683, U19AI095230, P01AI106683, AI-095230)
- Office of Research on Women's Health
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- asthma, DNA methylation, asthma endotypes, airway epithelial cells, epigenetics, genetic risk, host-environment interactions, asthma pathogenesis, transcriptome, lung cells
- MeSH terms
- Adult, Asthma, Epithelial Cells, Female, Humans, Lung, Male, Middle Aged, Gene Expression, Case-Control Studies, DNA Methylation, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Epigenesis, Genetic, Transcriptome
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