Polychlorinated biphenyl exposure and DNA methylation in the Anniston Community Health Survey
Anniston, Alabama was home to a major polychlorinated biphenyl (PCB) production facility from 1929 until 1971. The Anniston Community Health Survey I and II (ACHS-I 2005–2007, ACHS-II 2013–2014) were conducted to explore the effects of PCB exposures. In this report we examined associations between P...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2020-04-01
|
| Series: | Epigenetics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15592294.2019.1666654 |
| _version_ | 1827811593157607424 |
|---|---|
| author | Gary S. Pittman Xuting Wang Michelle R. Campbell Sherry J. Coulter James R. Olson Marian Pavuk Linda S. Birnbaum Douglas A. Bell |
| author_facet | Gary S. Pittman Xuting Wang Michelle R. Campbell Sherry J. Coulter James R. Olson Marian Pavuk Linda S. Birnbaum Douglas A. Bell |
| author_sort | Gary S. Pittman |
| collection | DOAJ |
| description | Anniston, Alabama was home to a major polychlorinated biphenyl (PCB) production facility from 1929 until 1971. The Anniston Community Health Survey I and II (ACHS-I 2005–2007, ACHS-II 2013–2014) were conducted to explore the effects of PCB exposures. In this report we examined associations between PCB exposure and DNA methylation in whole blood using EPIC arrays (ACHS-I, n = 518; ACHS-II, n = 299). For both cohorts, 35 PCBs were measured in serum. We modelled methylation versus PCB wet-weight concentrations for: the sum of 35 PCBs, mono-ortho substituted PCBs, di-ortho substituted PCBs, tri/tetra-ortho substituted PCBs, oestrogenic PCBs, and antiestrogenic PCBs. Using robust multivariable linear regression, we adjusted for age, race, sex, smoking, total lipids, and six blood cell-type percentages. We carried out a two-stage analysis; discovery in ACHS-I followed by replication in ACHS-II. In ACHS-I, we identified 28 associations (17 unique CpGs) at p ≤ 6.70E-08 and 369 associations (286 unique CpGs) at FDR p ≤ 5.00E-02. A large proportion of the genes have been observed to interact with PCBs or dioxins in model studies. Among the 28 genome-wide significant CpG/PCB associations, 14 displayed replicated directional effects in ACHS-II; however, only one in ACHS-II was statistically significant at p ≤ 1.70E-04. While we identified many novel CpGs significantly associated with PCB exposures in ACHS-I, the differential methylation was modest and the effect was attenuated seven years later in ACHS-II, suggesting a lack of persistence of the associations between PCB exposures and altered DNA methylation in blood cells. |
| first_indexed | 2024-03-11T23:07:01Z |
| format | Article |
| id | doaj.art-f6d98641c74d48e6ab1d737e5c152f16 |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:07:01Z |
| publishDate | 2020-04-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-f6d98641c74d48e6ab1d737e5c152f162023-09-21T13:09:22ZengTaylor & Francis GroupEpigenetics1559-22941559-23082020-04-0115433735710.1080/15592294.2019.16666541666654Polychlorinated biphenyl exposure and DNA methylation in the Anniston Community Health SurveyGary S. Pittman0Xuting Wang1Michelle R. Campbell2Sherry J. Coulter3James R. Olson4Marian Pavuk5Linda S. Birnbaum6Douglas A. Bell7National Institute of Environmental Health SciencesNational Institute of Environmental Health SciencesNational Institute of Environmental Health SciencesNational Cancer Institute at NIEHS, RTPUniversity at BuffaloATSDR, Center for Disease ControlNational Cancer Institute at NIEHS, RTPNational Institute of Environmental Health SciencesAnniston, Alabama was home to a major polychlorinated biphenyl (PCB) production facility from 1929 until 1971. The Anniston Community Health Survey I and II (ACHS-I 2005–2007, ACHS-II 2013–2014) were conducted to explore the effects of PCB exposures. In this report we examined associations between PCB exposure and DNA methylation in whole blood using EPIC arrays (ACHS-I, n = 518; ACHS-II, n = 299). For both cohorts, 35 PCBs were measured in serum. We modelled methylation versus PCB wet-weight concentrations for: the sum of 35 PCBs, mono-ortho substituted PCBs, di-ortho substituted PCBs, tri/tetra-ortho substituted PCBs, oestrogenic PCBs, and antiestrogenic PCBs. Using robust multivariable linear regression, we adjusted for age, race, sex, smoking, total lipids, and six blood cell-type percentages. We carried out a two-stage analysis; discovery in ACHS-I followed by replication in ACHS-II. In ACHS-I, we identified 28 associations (17 unique CpGs) at p ≤ 6.70E-08 and 369 associations (286 unique CpGs) at FDR p ≤ 5.00E-02. A large proportion of the genes have been observed to interact with PCBs or dioxins in model studies. Among the 28 genome-wide significant CpG/PCB associations, 14 displayed replicated directional effects in ACHS-II; however, only one in ACHS-II was statistically significant at p ≤ 1.70E-04. While we identified many novel CpGs significantly associated with PCB exposures in ACHS-I, the differential methylation was modest and the effect was attenuated seven years later in ACHS-II, suggesting a lack of persistence of the associations between PCB exposures and altered DNA methylation in blood cells.http://dx.doi.org/10.1080/15592294.2019.1666654polychlorinated biphenyl (pcb)persistent organic pollutant (pop)2378-tetrachlorodibenzodioxin (tcdd/dioxin)polychlorinated dibenzo-p-dioxins (pcdds)polychlorinated dibenzofurans (pcdfs)dna methylationanniston community health survey (achs) |
| spellingShingle | Gary S. Pittman Xuting Wang Michelle R. Campbell Sherry J. Coulter James R. Olson Marian Pavuk Linda S. Birnbaum Douglas A. Bell Polychlorinated biphenyl exposure and DNA methylation in the Anniston Community Health Survey Epigenetics polychlorinated biphenyl (pcb) persistent organic pollutant (pop) 2 3 7 8-tetrachlorodibenzodioxin (tcdd/dioxin) polychlorinated dibenzo-p-dioxins (pcdds) polychlorinated dibenzofurans (pcdfs) dna methylation anniston community health survey (achs) |
| title | Polychlorinated biphenyl exposure and DNA methylation in the Anniston Community Health Survey |
| title_full | Polychlorinated biphenyl exposure and DNA methylation in the Anniston Community Health Survey |
| title_fullStr | Polychlorinated biphenyl exposure and DNA methylation in the Anniston Community Health Survey |
| title_full_unstemmed | Polychlorinated biphenyl exposure and DNA methylation in the Anniston Community Health Survey |
| title_short | Polychlorinated biphenyl exposure and DNA methylation in the Anniston Community Health Survey |
| title_sort | polychlorinated biphenyl exposure and dna methylation in the anniston community health survey |
| topic | polychlorinated biphenyl (pcb) persistent organic pollutant (pop) 2 3 7 8-tetrachlorodibenzodioxin (tcdd/dioxin) polychlorinated dibenzo-p-dioxins (pcdds) polychlorinated dibenzofurans (pcdfs) dna methylation anniston community health survey (achs) |
| url | http://dx.doi.org/10.1080/15592294.2019.1666654 |
| work_keys_str_mv | AT garyspittman polychlorinatedbiphenylexposureanddnamethylationintheannistoncommunityhealthsurvey AT xutingwang polychlorinatedbiphenylexposureanddnamethylationintheannistoncommunityhealthsurvey AT michellercampbell polychlorinatedbiphenylexposureanddnamethylationintheannistoncommunityhealthsurvey AT sherryjcoulter polychlorinatedbiphenylexposureanddnamethylationintheannistoncommunityhealthsurvey AT jamesrolson polychlorinatedbiphenylexposureanddnamethylationintheannistoncommunityhealthsurvey AT marianpavuk polychlorinatedbiphenylexposureanddnamethylationintheannistoncommunityhealthsurvey AT lindasbirnbaum polychlorinatedbiphenylexposureanddnamethylationintheannistoncommunityhealthsurvey AT douglasabell polychlorinatedbiphenylexposureanddnamethylationintheannistoncommunityhealthsurvey |