Epigenome-wide association study reveals methylation pathways associated with childhood allergic sensitization
Epigenetic mechanisms integrate both genetic variability and environmental exposures. However, comprehensive epigenome-wide analysis has not been performed across major childhood allergic phenotypes. We examined the association of epigenome-wide DNA methylation in mid-childhood peripheral blood (Ill...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-05-01
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| Series: | Epigenetics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15592294.2019.1590085 |
| _version_ | 1827811532772212736 |
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| author | Cheng Peng Evelien R. Van Meel Andres Cardenas Sheryl L. Rifas-Shiman Abhijeet R. Sonawane Kimberly R. Glass Diane R. Gold Thomas A. Platts-Mills Xihong Lin Emily Oken Marie-France Hivert Andrea A. Baccarelli Nicolette W. De Jong Janine F. Felix Vincent W. Jaddoe Liesbeth Duijts Augusto A. Litonjua Dawn L. DeMeo |
| author_facet | Cheng Peng Evelien R. Van Meel Andres Cardenas Sheryl L. Rifas-Shiman Abhijeet R. Sonawane Kimberly R. Glass Diane R. Gold Thomas A. Platts-Mills Xihong Lin Emily Oken Marie-France Hivert Andrea A. Baccarelli Nicolette W. De Jong Janine F. Felix Vincent W. Jaddoe Liesbeth Duijts Augusto A. Litonjua Dawn L. DeMeo |
| author_sort | Cheng Peng |
| collection | DOAJ |
| description | Epigenetic mechanisms integrate both genetic variability and environmental exposures. However, comprehensive epigenome-wide analysis has not been performed across major childhood allergic phenotypes. We examined the association of epigenome-wide DNA methylation in mid-childhood peripheral blood (Illumina HumanMethyl450K) with mid-childhood atopic sensitization, environmental/inhalant and food allergen sensitization in 739 children in two birth cohorts (Project Viva–Boston, and the Generation R Study–Rotterdam). We performed covariate-adjusted epigenome-wide association meta-analysis and employed pathway and regional analyses of results. Seven-hundred and five methylation sites (505 genes) were significantly cross-sectionally associated with mid-childhood atopic sensitization, 1411 (905 genes) for environmental and 45 (36 genes) for food allergen sensitization (FDR<0.05). We observed differential methylation across multiple genes for all three phenotypes, including genes implicated previously in innate immunity (DICER1), eosinophilic esophagitis and sinusitis (SIGLEC8), the atopic march (AP5B1) and asthma (EPX, IL4, IL5RA, PRG2, SIGLEC8, CLU). In addition, most of the associated methylation marks for all three phenotypes occur in putative transcription factor binding motifs. Pathway analysis identified multiple methylation sites associated with atopic sensitization and environmental allergen sensitization located in/near genes involved in asthma, mTOR signaling, and inositol phosphate metabolism. We identified multiple differentially methylated regions associated with atopic sensitization (8 regions) and environmental allergen sensitization (26 regions). A number of nominally significant methylation sites in the cord blood analysis were epigenome-wide significant in the mid-childhood analysis, and we observed significant methylation – time interactions among a subset of sites examined. Our findings provide insights into epigenetic regulatory pathways as markers of childhood allergic sensitization. |
| first_indexed | 2024-03-11T23:06:20Z |
| format | Article |
| id | doaj.art-41aa43c92c09493c8f497cef800d0495 |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:06:20Z |
| publishDate | 2019-05-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-41aa43c92c09493c8f497cef800d04952023-09-21T13:09:21ZengTaylor & Francis GroupEpigenetics1559-22941559-23082019-05-0114544546610.1080/15592294.2019.15900851590085Epigenome-wide association study reveals methylation pathways associated with childhood allergic sensitizationCheng Peng0Evelien R. Van Meel1Andres Cardenas2Sheryl L. Rifas-Shiman3Abhijeet R. Sonawane4Kimberly R. Glass5Diane R. Gold6Thomas A. Platts-Mills7Xihong Lin8Emily Oken9Marie-France Hivert10Andrea A. Baccarelli11Nicolette W. De Jong12Janine F. Felix13Vincent W. Jaddoe14Liesbeth Duijts15Augusto A. Litonjua16Dawn L. DeMeo17Brigham and Women’s Hospital, Harvard Medical SchoolUniversity Medical Center RotterdamUniversity of California, Berkeley, School of Public HealthHarvard Medical School and Harvard Pilgrim Health Care InstituteBrigham and Women’s Hospital, Harvard Medical SchoolBrigham and Women’s Hospital, Harvard Medical SchoolBrigham and Women’s Hospital, Harvard Medical SchoolUniversity of Virginia School of MedicineHarvard T.H Chan School of Public HealthHarvard Medical School and Harvard Pilgrim Health Care InstituteHarvard Medical School and Harvard Pilgrim Health Care InstituteColumbia University Mailman School of Public HealthUniversity Medical Center RotterdamUniversity Medical Center RotterdamUniversity Medical Center RotterdamUniversity Medical Center RotterdamUniversity of Rochester Medical CenterBrigham and Women’s Hospital, Harvard Medical SchoolEpigenetic mechanisms integrate both genetic variability and environmental exposures. However, comprehensive epigenome-wide analysis has not been performed across major childhood allergic phenotypes. We examined the association of epigenome-wide DNA methylation in mid-childhood peripheral blood (Illumina HumanMethyl450K) with mid-childhood atopic sensitization, environmental/inhalant and food allergen sensitization in 739 children in two birth cohorts (Project Viva–Boston, and the Generation R Study–Rotterdam). We performed covariate-adjusted epigenome-wide association meta-analysis and employed pathway and regional analyses of results. Seven-hundred and five methylation sites (505 genes) were significantly cross-sectionally associated with mid-childhood atopic sensitization, 1411 (905 genes) for environmental and 45 (36 genes) for food allergen sensitization (FDR<0.05). We observed differential methylation across multiple genes for all three phenotypes, including genes implicated previously in innate immunity (DICER1), eosinophilic esophagitis and sinusitis (SIGLEC8), the atopic march (AP5B1) and asthma (EPX, IL4, IL5RA, PRG2, SIGLEC8, CLU). In addition, most of the associated methylation marks for all three phenotypes occur in putative transcription factor binding motifs. Pathway analysis identified multiple methylation sites associated with atopic sensitization and environmental allergen sensitization located in/near genes involved in asthma, mTOR signaling, and inositol phosphate metabolism. We identified multiple differentially methylated regions associated with atopic sensitization (8 regions) and environmental allergen sensitization (26 regions). A number of nominally significant methylation sites in the cord blood analysis were epigenome-wide significant in the mid-childhood analysis, and we observed significant methylation – time interactions among a subset of sites examined. Our findings provide insights into epigenetic regulatory pathways as markers of childhood allergic sensitization.http://dx.doi.org/10.1080/15592294.2019.1590085epigenome-wide dna methylationchildhood allergychildhood environmental allergychildhood food allergyallergic marchbirth cohortsmeta analysisregional analysis |
| spellingShingle | Cheng Peng Evelien R. Van Meel Andres Cardenas Sheryl L. Rifas-Shiman Abhijeet R. Sonawane Kimberly R. Glass Diane R. Gold Thomas A. Platts-Mills Xihong Lin Emily Oken Marie-France Hivert Andrea A. Baccarelli Nicolette W. De Jong Janine F. Felix Vincent W. Jaddoe Liesbeth Duijts Augusto A. Litonjua Dawn L. DeMeo Epigenome-wide association study reveals methylation pathways associated with childhood allergic sensitization Epigenetics epigenome-wide dna methylation childhood allergy childhood environmental allergy childhood food allergy allergic march birth cohorts meta analysis regional analysis |
| title | Epigenome-wide association study reveals methylation pathways associated with childhood allergic sensitization |
| title_full | Epigenome-wide association study reveals methylation pathways associated with childhood allergic sensitization |
| title_fullStr | Epigenome-wide association study reveals methylation pathways associated with childhood allergic sensitization |
| title_full_unstemmed | Epigenome-wide association study reveals methylation pathways associated with childhood allergic sensitization |
| title_short | Epigenome-wide association study reveals methylation pathways associated with childhood allergic sensitization |
| title_sort | epigenome wide association study reveals methylation pathways associated with childhood allergic sensitization |
| topic | epigenome-wide dna methylation childhood allergy childhood environmental allergy childhood food allergy allergic march birth cohorts meta analysis regional analysis |
| url | http://dx.doi.org/10.1080/15592294.2019.1590085 |
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