Humans are exposed to chemicals such as brominated flame retardants (BFRs) at unprecedented levels, and a wide variety of health effects are attributed to such exposures. However, the biological mechanisms that link exposures to its consequences remain unknown. An industrial accident in the 1970's exposed over 4000 individuals in rural Michigan to polybrominated biphenyl (PBB), a BFR that was present in the food supply for years prior to detection and management. Health effects are still evident in these individuals and their children. Because this population has been assessed regularly since the exposure, it is an ideal group in which to examine the molecular mechanisms that contribute to susceptibility, vulnerability and health effects. The project goals are to: 1) identify the genetic variants that associate with the rate of PBB elimination over time, 2) identif epigenetic patterns that associate with PBB exposure, 3) integrate genetic and epigenetic datasets and identify complex gene-environment relationships in PBB exposed individuals and 4) evaluate the contribution PBB-associated genetic and epigenetic factors to endocrine-related consequences of exposure. We will leverage data generated as part of past and ongoing studies in the Michigan Polybrominated Biphenyl Cohort and characterize genetic and epigenetic variation in 2 PBB-exposed cohorts, a discovery cohort of 500 subjects exposed through living on or eating food from contaminated farms and a replication cohort of 200 subjects exposed through work at the Michigan Chemical Company that produced PBBs. This research will produce the largest and most comprehensive genetic dataset in subjects exposed to PBBs. We anticipate that this study will provide insight into how genetic variants and the environment interact in relation to PBB exposure and its health effects. We also anticipate the results of this study will be informative for studies of BFRs and other endocrine disrupting compounds with similar chemical properties.

Public Health Relevance

An industrial accident in the 1970's exposed over 4000 individuals in rural Michigan to polybrominated biphenyl (PBB), and the residents of this area are still experiencing substantial health effects because of that exposure. This project will examine sequence variants, epigenetic patterns and their interactive effects to identify factors that contribute to individual susceptibility, vulnerability and endocrine-related problems in this cohort. This study will generate a comprehensive genetic and epigenetic dataset in an extensively characterized cohort of provide insight into the biological mechanisms that link PBB exposures to endocrine-related health consequences and provide a relevant framework to evaluate compounds with similar chemical properties. PBB-exposed subjects and we anticipate that the results will provide insight into the biological mechanisms that link PBB exposures to endocrine-related health consequences and provide a relevant framework to evaluate compounds with similar chemical properties.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES024790-02
Application #
9149282
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Mcallister, Kimberly A
Project Start
2015-09-30
Project End
2019-07-31
Budget Start
2016-08-01
Budget End
2017-07-31
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Emory University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Jacobson, Melanie H; Howards, Penelope P; Darrow, Lyndsey A et al. (2018) Thyroid hormones and menstrual cycle function in a longitudinal cohort of premenopausal women. Paediatr Perinat Epidemiol 32:225-234
Curtis, Sarah W; Conneely, Karen N; Marder, Mary E et al. (2018) Intergenerational effects of endocrine-disrupting compounds: a review of the Michigan polybrominated biphenyl registry. Epigenomics 10:845-858
Jacobson, Melanie H; Darrow, Lyndsey A; Barr, Dana Boyd et al. (2017) Serum Polybrominated Biphenyls (PBBs) and Polychlorinated Biphenyls (PCBs) and Thyroid Function among Michigan Adults Several Decades after the 1973-1974 PBB Contamination of Livestock Feed. Environ Health Perspect 125:097020