Genome-wide DNA methylation differences and polychlorinated biphenyl (PCB) exposure in a US population

• Type of Material: Article
• Authors: Sarah W Curtis, Emory University; Dawayland O Cobb, Emory University; Varun Kilaru, Emory University; Metrecia L Terrell, Emory University; Elizabeth Marder, Emory University; Dana Barr, Emory University; Carmen Marsit, Emory University; Michele Marcus, Emory University; Karen Conneely, Emory University; Alicia Smith, Emory University
• Language: English
• Date: 2020-07-24
• Publisher: TAYLOR & FRANCIS INC
• Publication Version: Final Published Version
• Copyright Statement: © 2020 Informa UK Limited, trading as Taylor & Francis Group
• Final Published Version (URL): http://dx.doi.org/10.1080/15592294.2020.1795605
• Title of Journal or Parent Work: EPIGENETICS
• Volume: 16
• Issue: 3
• Start Page: 338
• End Page: 352
• Grant/Funding Information: Additional support was provided by the Georgia Clinical & Translational Science Alliance of the National Institutes of Health under Award Number [UL1TR002378].; The content is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institutes of Health.; This study was supported in part by the Emory Integrated Genomics Core (EIGC), which is subsidized by the Emory University School of Medicine and is one of the Emory Integrated Core Facilities.; This work was supported by the National Institute of Environmental Health Sciences [NIEHS; R01ES024790, R01ES025775, R24ES028528, P30ES019776] and the National Institute of General Medical Sciences [T32GM008490].
• Keywords: Life Sciences & Biomedicine; SERUM; EDC; PERSISTENT ORGANIC POLLUTANTS; Science & Technology; immune function; ELIMINATION HALF-LIVES; epigenome-wide association study; DISCOVERY; Biochemistry & Molecular Biology; INFLAMMATION; HORMONES; POLYBROMINATED DIPHENYL ETHERS; EWAS; Genetics & Heredity; EXPRESSION; ASSOCIATION; ANNOTATION; endocrine-disrupting compound; Epigenetics
• Research Categories: Health Sciences, Obstetrics and Gynecology; Environmental Sciences; Health Sciences, Epidemiology

Abstract

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.