Sex-specific DNA methylation differences in people exposed to polybrominated biphenyl

Abstract

Aim: Michigan residents were exposed to polybrominated biphenyls (PBBs) when it was accidentally added to the food supply. Highly exposed individuals report sex-specific health problems, but the underlying biological mechanism behind these different health risks is not known. Materials and methods: DNA methylation in blood from 381 women and 277 men with PBB exposure was analyzed with the MethylationEPIC BeadChip. Results: 675 CpGs were associated with PBBs levels in males, while only 17 CpGs were associated in females (false discovery rate 0.05). No CpGs were associated in both sexes. These CpGs were enriched in different functional regions and transcription factor binding sites in each sex. Conclusion: Exposure to PBBs may have sex-specific effects on the epigenome that may underlie sex-specific adverse health outcomes.

Keywords::

• DNA methylation
• EDC
• endocrine-disrupting compound
• environmental health
• epigenetics
• epigenome-wide association study
• EWAS
• polybrominated biphenyl
• sex differences
• sex specific

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2019-0179

Acknowledgments

We are grateful to the members of the Michigan polybrominated biphenyl (PBB) Registry for their participation and engagement with research studies over the past 40 years, the Michigan Department of Health and Human Services, which had the foresight to create the Registry and to our community partners (PBB Citizen Advisory Board, Pine River Superfund Citizen Task Force and the Mid-Michigan District Health Department) who continue to provide guidance and insight to the Michigan PBB Research.

Financial & competing interest disclosure

This work was supported by the National Institute of Environmental Health Sciences (NIEHS; R01ES024790, R01ES025775, R24ES028528 and P30ES019776) and the National Institute of General Medical Sciences (T32GM008490). 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. 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. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

Study protocols were approved by the Institutional Review Board at Emory University. Informed consent was obtained from all participants involved.

Data sharing statement

The DNA methylation data can be accessed on NCBI’s Gene Expression Omnibus (GSE116339).