ABSTRACT
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.
Acknowledgments
We recognize Dr. Stephen T. Mennemeyer of University of Alabama Birmingham for his study contributions. We express gratitude to the study participants in the ACHS-I and ACHS-II cohorts. We thank the Cancer Genomics Research Laboratory at the National Cancer Institute (Rockville, MD) for methylation array analysis. We thank Andeas Sjödin and Richard Jones of the Center for Disease Control and Prevention’s Division of Laboratory Sciences within the National Center for Environmental Health for the analyses of polychlorinated biphenyls and dioxins. We acknowledge Kevin E. Gerrish and Joetta Hitchcock-Smith, NIEHS Molecular Genomics Core Laboratory for ACHS-II DNA extractions (RTP, NC). We appreciated the help of Dr. Phillip Grandjean and colleagues, Department of Environmental Health, Harvard T.H. Chan School of Public Health in providing the list of CpGs from the Leung et al. study. We also thank Suzanne N. Martos (NIEHS, RTP, NC) for suggestions and feedback regarding data analysis and presentation, and Leonardo E. Albertini Sanchez (NIEHS, RTP, NC) for assistance with copy editing.
Disclosure statement
J.R. Olson served as an expert witness for the plaintiffs in legal actions regarding the residents of Anniston, Alabama being exposed to PCBs. The other authors declare that they have no competing interests.
Supplementary material
Supplemental data for this article can be accessed here.