Genome-wide DNA methylation differences and polychlorinated biphenyl (PCB) exposure in a US population
Exposure to polychlorinated biphenyls (PCBs), an endocrine-disrupting compound, is ubiquitous despite decades-old bans on the manufacture and use of PCBs. Increased exposure to PCBs is associated with adverse health consequences throughout life, including type 2 diabetes and cancer. PCB exposure is...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-03-01
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| Series: | Epigenetics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15592294.2020.1795605 |
| _version_ | 1827811463981432832 |
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| author | Sarah W. Curtis Dawayland O. Cobb Varun Kilaru Metrecia L. Terrell M. Elizabeth Marder Dana Boyd Barr Carmen J. Marsit Michele Marcus Karen N. Conneely Alicia K. Smith |
| author_facet | Sarah W. Curtis Dawayland O. Cobb Varun Kilaru Metrecia L. Terrell M. Elizabeth Marder Dana Boyd Barr Carmen J. Marsit Michele Marcus Karen N. Conneely Alicia K. Smith |
| author_sort | Sarah W. Curtis |
| collection | DOAJ |
| description | Exposure to polychlorinated biphenyls (PCBs), an endocrine-disrupting compound, is ubiquitous despite decades-old bans on the manufacture and use of PCBs. Increased exposure to PCBs is associated with adverse health consequences throughout life, including type 2 diabetes and cancer. PCB exposure is also associated with alterations in epigenetic marks and gene transcription, which could lead to adverse health outcomes, but many of these are population-specific. To further investigate the association between PCB and epigenetic marks, DNA methylation was measured at 787,684 CpG sites in 641 peripheral blood samples from the Michigan Polybrominated Biphenyl (PBB) Registry. 1345 CpGs were associated with increased total PCB level after controlling for age, sex, and 24 surrogate variables (FDR < 0.05). These CpGs were enriched in active promoter and transcription associated regions (p < 0.05), and in regions around the binding sites for transcription factors involved in xenobiotic metabolism and immune function (FDR < 0.05). PCB exposure also associated with proportions of CD4T, NK, and granulocyte cell types, and with the neutrophil to lymphocyte ratio (NLR) (p < 0.05), and the estimated effect sizes of PCB on the epigenome were correlated with the effect sizes previously reported in an epigenome-wide study of C-reactive protein (r = 0.29; p = 2.22e-5), supporting previous studies on the association between PCB and immune dysfunction. These results indicate that PCB exposure is associated with differences in epigenetic marks in active regions of the genome, and future work should investigate whether these may mediate the association between PCB and health consequences. |
| first_indexed | 2024-03-11T23:05:31Z |
| format | Article |
| id | doaj.art-7398b175a31b41458701e21d9175945e |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:05:31Z |
| publishDate | 2021-03-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-7398b175a31b41458701e21d9175945e2023-09-21T13:09:24ZengTaylor & Francis GroupEpigenetics1559-22941559-23082021-03-0116333835210.1080/15592294.2020.17956051795605Genome-wide DNA methylation differences and polychlorinated biphenyl (PCB) exposure in a US populationSarah W. Curtis0Dawayland O. Cobb1Varun Kilaru2Metrecia L. Terrell3M. Elizabeth Marder4Dana Boyd Barr5Carmen J. Marsit6Michele Marcus7Karen N. Conneely8Alicia K. Smith9Emory University School of MedicineEmory University School of MedicineEmory University School of MedicineEmory University Rollins School of Public HealthEmory University Rollins School of Public HealthEmory University Rollins School of Public HealthEmory University Rollins School of Public HealthEmory University Rollins School of Public HealthEmory University School of MedicineEmory University School of MedicineExposure to polychlorinated biphenyls (PCBs), an endocrine-disrupting compound, is ubiquitous despite decades-old bans on the manufacture and use of PCBs. Increased exposure to PCBs is associated with adverse health consequences throughout life, including type 2 diabetes and cancer. PCB exposure is also associated with alterations in epigenetic marks and gene transcription, which could lead to adverse health outcomes, but many of these are population-specific. To further investigate the association between PCB and epigenetic marks, DNA methylation was measured at 787,684 CpG sites in 641 peripheral blood samples from the Michigan Polybrominated Biphenyl (PBB) Registry. 1345 CpGs were associated with increased total PCB level after controlling for age, sex, and 24 surrogate variables (FDR < 0.05). These CpGs were enriched in active promoter and transcription associated regions (p < 0.05), and in regions around the binding sites for transcription factors involved in xenobiotic metabolism and immune function (FDR < 0.05). PCB exposure also associated with proportions of CD4T, NK, and granulocyte cell types, and with the neutrophil to lymphocyte ratio (NLR) (p < 0.05), and the estimated effect sizes of PCB on the epigenome were correlated with the effect sizes previously reported in an epigenome-wide study of C-reactive protein (r = 0.29; p = 2.22e-5), supporting previous studies on the association between PCB and immune dysfunction. These results indicate that PCB exposure is associated with differences in epigenetic marks in active regions of the genome, and future work should investigate whether these may mediate the association between PCB and health consequences.http://dx.doi.org/10.1080/15592294.2020.1795605epigeneticsewasepigenome-wide association studyedcendocrine-disrupting compoundimmune function |
| spellingShingle | Sarah W. Curtis Dawayland O. Cobb Varun Kilaru Metrecia L. Terrell M. Elizabeth Marder Dana Boyd Barr Carmen J. Marsit Michele Marcus Karen N. Conneely Alicia K. Smith Genome-wide DNA methylation differences and polychlorinated biphenyl (PCB) exposure in a US population Epigenetics epigenetics ewas epigenome-wide association study edc endocrine-disrupting compound immune function |
| title | Genome-wide DNA methylation differences and polychlorinated biphenyl (PCB) exposure in a US population |
| title_full | Genome-wide DNA methylation differences and polychlorinated biphenyl (PCB) exposure in a US population |
| title_fullStr | Genome-wide DNA methylation differences and polychlorinated biphenyl (PCB) exposure in a US population |
| title_full_unstemmed | Genome-wide DNA methylation differences and polychlorinated biphenyl (PCB) exposure in a US population |
| title_short | Genome-wide DNA methylation differences and polychlorinated biphenyl (PCB) exposure in a US population |
| title_sort | genome wide dna methylation differences and polychlorinated biphenyl pcb exposure in a us population |
| topic | epigenetics ewas epigenome-wide association study edc endocrine-disrupting compound immune function |
| url | http://dx.doi.org/10.1080/15592294.2020.1795605 |
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