Epigenome-wide association study of total serum immunoglobulin E in children: a life course approach
Abstract Background IgE-mediated sensitization may be epigenetically programmed in utero, but early childhood environment may further alter complex traits and disease phenotypes through epigenetic plasticity. However, the epigenomic footprint underpinning IgE-mediated type-I hypersensitivity has not...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-04-01
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| Series: | Clinical Epigenetics |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13148-018-0488-x |
| _version_ | 1818675762834702336 |
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| author | Cheng Peng Andres Cardenas Sheryl L. Rifas-Shiman Marie-France Hivert Diane R. Gold Thomas A. Platts-Mills Xihong Lin Emily Oken Andrea A. Baccarelli Augusto A. Litonjua Dawn L. DeMeo |
| author_facet | Cheng Peng Andres Cardenas Sheryl L. Rifas-Shiman Marie-France Hivert Diane R. Gold Thomas A. Platts-Mills Xihong Lin Emily Oken Andrea A. Baccarelli Augusto A. Litonjua Dawn L. DeMeo |
| author_sort | Cheng Peng |
| collection | DOAJ |
| description | Abstract Background IgE-mediated sensitization may be epigenetically programmed in utero, but early childhood environment may further alter complex traits and disease phenotypes through epigenetic plasticity. However, the epigenomic footprint underpinning IgE-mediated type-I hypersensitivity has not been well-understood, especially under a longitudinal early-childhood life-course framework. Methods We used epigenome-wide DNA methylation (IlluminaHumanMethylation450 BeadChip) in cord blood and mid-childhood peripheral blood to investigate pre- and post-natal methylation marks associated with mid-childhood (age 6.7–10.2) total serum IgE levels in 217 mother-child pairs in Project Viva—a prospective longitudinal pre-birth cohort in eastern Massachusetts, USA. We identified methylation sites associated with IgE using covariate-adjusted robust linear regressions. Results Nineteen methylation marks in cord blood were associated with IgE in mid-childhood (FDR < 0.05) in genes implicated in cell signaling, growth, and development. Among these, two methylation sites (C7orf50, ZAR1) remained robust after the adjustment for the change in DNA methylation from birth to mid-childhood (FDR < 0.05). An analysis of the change in methylation between cord blood and mid-childhood DNA (Δ-DNAm) identified 395 methylation marks in 272 genes associated with mid-childhood IgE (FDR < 0.05), with multiple sites located within ACOT7 (4 sites), EPX (5 sites), EVL (3 sites), KSR1 (4 sites), ZFPM1 (3 sites), and ZNF862 (3 sites). Several of these methylation loci were previously associated with asthma (ADAM19, EPX, IL4, IL5RA, and PRG2). Conclusion This study identified fetally programmed and mid-childhood methylation signals associated with mid-childhood IgE. Epigenetic priming during fetal development and early childhood likely plays an important role in IgE-mediated type-I hypersensitivity. |
| first_indexed | 2024-12-17T08:32:44Z |
| format | Article |
| id | doaj.art-fdd915d7488740fc872bf94af618577f |
| institution | Directory Open Access Journal |
| issn | 1868-7075 1868-7083 |
| language | English |
| last_indexed | 2024-12-17T08:32:44Z |
| publishDate | 2018-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj.art-fdd915d7488740fc872bf94af618577f2022-12-21T21:56:33ZengBMCClinical Epigenetics1868-70751868-70832018-04-0110111410.1186/s13148-018-0488-xEpigenome-wide association study of total serum immunoglobulin E in children: a life course approachCheng Peng0Andres Cardenas1Sheryl L. Rifas-Shiman2Marie-France Hivert3Diane R. Gold4Thomas A. Platts-Mills5Xihong Lin6Emily Oken7Andrea A. Baccarelli8Augusto A. Litonjua9Dawn L. DeMeo10Channing Division of Network Medicine and the Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical SchoolDivision of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care InstituteDivision of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care InstituteDivision of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care InstituteChanning Division of Network Medicine and the Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical SchoolDivision of Allergy and Clinical Immunology, University of Virginia School of MedicineDepartment of Biostatistics, Harvard T. H. Chan School of Public HealthDivision of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care InstituteDepartment of Environmental Health Sciences, Columbia University Mailman School of Public HealthChanning Division of Network Medicine and the Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical SchoolChanning Division of Network Medicine and the Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical SchoolAbstract Background IgE-mediated sensitization may be epigenetically programmed in utero, but early childhood environment may further alter complex traits and disease phenotypes through epigenetic plasticity. However, the epigenomic footprint underpinning IgE-mediated type-I hypersensitivity has not been well-understood, especially under a longitudinal early-childhood life-course framework. Methods We used epigenome-wide DNA methylation (IlluminaHumanMethylation450 BeadChip) in cord blood and mid-childhood peripheral blood to investigate pre- and post-natal methylation marks associated with mid-childhood (age 6.7–10.2) total serum IgE levels in 217 mother-child pairs in Project Viva—a prospective longitudinal pre-birth cohort in eastern Massachusetts, USA. We identified methylation sites associated with IgE using covariate-adjusted robust linear regressions. Results Nineteen methylation marks in cord blood were associated with IgE in mid-childhood (FDR < 0.05) in genes implicated in cell signaling, growth, and development. Among these, two methylation sites (C7orf50, ZAR1) remained robust after the adjustment for the change in DNA methylation from birth to mid-childhood (FDR < 0.05). An analysis of the change in methylation between cord blood and mid-childhood DNA (Δ-DNAm) identified 395 methylation marks in 272 genes associated with mid-childhood IgE (FDR < 0.05), with multiple sites located within ACOT7 (4 sites), EPX (5 sites), EVL (3 sites), KSR1 (4 sites), ZFPM1 (3 sites), and ZNF862 (3 sites). Several of these methylation loci were previously associated with asthma (ADAM19, EPX, IL4, IL5RA, and PRG2). Conclusion This study identified fetally programmed and mid-childhood methylation signals associated with mid-childhood IgE. Epigenetic priming during fetal development and early childhood likely plays an important role in IgE-mediated type-I hypersensitivity.http://link.springer.com/article/10.1186/s13148-018-0488-xEpigenome-wide association studiesTotal serum IgELife course analysis |
| spellingShingle | Cheng Peng Andres Cardenas Sheryl L. Rifas-Shiman Marie-France Hivert Diane R. Gold Thomas A. Platts-Mills Xihong Lin Emily Oken Andrea A. Baccarelli Augusto A. Litonjua Dawn L. DeMeo Epigenome-wide association study of total serum immunoglobulin E in children: a life course approach Clinical Epigenetics Epigenome-wide association studies Total serum IgE Life course analysis |
| title | Epigenome-wide association study of total serum immunoglobulin E in children: a life course approach |
| title_full | Epigenome-wide association study of total serum immunoglobulin E in children: a life course approach |
| title_fullStr | Epigenome-wide association study of total serum immunoglobulin E in children: a life course approach |
| title_full_unstemmed | Epigenome-wide association study of total serum immunoglobulin E in children: a life course approach |
| title_short | Epigenome-wide association study of total serum immunoglobulin E in children: a life course approach |
| title_sort | epigenome wide association study of total serum immunoglobulin e in children a life course approach |
| topic | Epigenome-wide association studies Total serum IgE Life course analysis |
| url | http://link.springer.com/article/10.1186/s13148-018-0488-x |
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