Exposure to polybrominated biphenyl (PBB) associates with genome-wide DNA methylation differences in peripheral blood
In 1973, Michigan residents were exposed to polybrominated biphenyl (PBB) when it was accidentally added to farm animal feed. Highly exposed individuals and their children have experienced endocrine-related health problems, though the underlying mechanism behind these remains unknown. We investigate...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-01-01
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| Series: | Epigenetics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15592294.2019.1565590 |
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| author | Sarah W. Curtis Dawayland O. Cobb Varun Kilaru Metrecia L. Terrell Elizabeth M. Kennedy 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 Elizabeth M. Kennedy 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 | In 1973, Michigan residents were exposed to polybrominated biphenyl (PBB) when it was accidentally added to farm animal feed. Highly exposed individuals and their children have experienced endocrine-related health problems, though the underlying mechanism behind these remains unknown. We investigated whether PBB exposure is associated with variation in DNA methylation in peripheral blood samples from 658 participants of the Michigan PBB registry using the MethylationEPIC BeadChip, as well as investigated what the potential function of the affected regions are and whether these epigenetic marks are known to associate with endocrine system pathways. After multiple test correction (FDR <0.05), 1890 CpG sites associated with total PBB levels. These CpGs were not enriched in any particular biological pathway, but were enriched in enhancer and insulator regions, and depleted in regions near the transcription start site or in CpG islands (p < 0.05). They were also more likely to be in ARNT and ESR2 transcription factor binding sites (p = 3.27e-23 and p = 1.62e-6, respectively), and there was significant overlap between CpGs associated with PBB and CpGs associated with estrogen (p < 2.2e-16). PBB-associated CpGs were also enriched for CpGs known to be associated with gene expression in blood (eQTMs) (p < 0.05). These eQTMs were enriched for pathways related to immune function and endocrine-related autoimmune disease (FDR <0.05). These results indicate that exposure to PBB is associated with differences in epigenetic marks that suggest that it is acting similarly to estrogen and is associated with dysregulated immune system pathways. |
| first_indexed | 2024-03-11T23:06:39Z |
| format | Article |
| id | doaj.art-8bd8b11744b64ac2a0ecb0714e1496db |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:06:39Z |
| publishDate | 2019-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-8bd8b11744b64ac2a0ecb0714e1496db2023-09-21T13:09:21ZengTaylor & Francis GroupEpigenetics1559-22941559-23082019-01-01141526610.1080/15592294.2019.15655901565590Exposure to polybrominated biphenyl (PBB) associates with genome-wide DNA methylation differences in peripheral bloodSarah W. Curtis0Dawayland O. Cobb1Varun Kilaru2Metrecia L. Terrell3Elizabeth M. Kennedy4M. Elizabeth Marder5Dana Boyd Barr6Carmen J. Marsit7Michele Marcus8Karen N. Conneely9Alicia K. Smith10Emory 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 Rollins School of Public HealthEmory University School of MedicineEmory University School of MedicineIn 1973, Michigan residents were exposed to polybrominated biphenyl (PBB) when it was accidentally added to farm animal feed. Highly exposed individuals and their children have experienced endocrine-related health problems, though the underlying mechanism behind these remains unknown. We investigated whether PBB exposure is associated with variation in DNA methylation in peripheral blood samples from 658 participants of the Michigan PBB registry using the MethylationEPIC BeadChip, as well as investigated what the potential function of the affected regions are and whether these epigenetic marks are known to associate with endocrine system pathways. After multiple test correction (FDR <0.05), 1890 CpG sites associated with total PBB levels. These CpGs were not enriched in any particular biological pathway, but were enriched in enhancer and insulator regions, and depleted in regions near the transcription start site or in CpG islands (p < 0.05). They were also more likely to be in ARNT and ESR2 transcription factor binding sites (p = 3.27e-23 and p = 1.62e-6, respectively), and there was significant overlap between CpGs associated with PBB and CpGs associated with estrogen (p < 2.2e-16). PBB-associated CpGs were also enriched for CpGs known to be associated with gene expression in blood (eQTMs) (p < 0.05). These eQTMs were enriched for pathways related to immune function and endocrine-related autoimmune disease (FDR <0.05). These results indicate that exposure to PBB is associated with differences in epigenetic marks that suggest that it is acting similarly to estrogen and is associated with dysregulated immune system pathways.http://dx.doi.org/10.1080/15592294.2019.1565590endocrine-disrupting compoundepigenome-wide association study (ewas)dna methylationpolybrominated biphenylenvironmental healthepigenetics |
| spellingShingle | Sarah W. Curtis Dawayland O. Cobb Varun Kilaru Metrecia L. Terrell Elizabeth M. Kennedy M. Elizabeth Marder Dana Boyd Barr Carmen J. Marsit Michele Marcus Karen N. Conneely Alicia K. Smith Exposure to polybrominated biphenyl (PBB) associates with genome-wide DNA methylation differences in peripheral blood Epigenetics endocrine-disrupting compound epigenome-wide association study (ewas) dna methylation polybrominated biphenyl environmental health epigenetics |
| title | Exposure to polybrominated biphenyl (PBB) associates with genome-wide DNA methylation differences in peripheral blood |
| title_full | Exposure to polybrominated biphenyl (PBB) associates with genome-wide DNA methylation differences in peripheral blood |
| title_fullStr | Exposure to polybrominated biphenyl (PBB) associates with genome-wide DNA methylation differences in peripheral blood |
| title_full_unstemmed | Exposure to polybrominated biphenyl (PBB) associates with genome-wide DNA methylation differences in peripheral blood |
| title_short | Exposure to polybrominated biphenyl (PBB) associates with genome-wide DNA methylation differences in peripheral blood |
| title_sort | exposure to polybrominated biphenyl pbb associates with genome wide dna methylation differences in peripheral blood |
| topic | endocrine-disrupting compound epigenome-wide association study (ewas) dna methylation polybrominated biphenyl environmental health epigenetics |
| url | http://dx.doi.org/10.1080/15592294.2019.1565590 |
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