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The Science of Gene-Environment Interaction at the Centers for Disease Control and Prevention and Agency for Toxic Substances and Disease Registry

['Stephanie Foster', 'Office Of Innovation And Analytics', 'Agency For Toxic Substances And Disease Registry', 'Marta Gwinn', 'Wei Yu', 'Muin J. Khoury', 'Office Of Genomics', 'Precision Public Health', 'Centers For Disease Control']

Date: 2021-10-18 00:00:00

Now, more than ever, we are aware that our environment has implications for our health. We are also learning more about the effects of inherited traits, such as blood type, on disease susceptibility and progression. Understanding the interactions between our environment and our genes and how they affect health outcomes offers a multitude of potential opportunities in public health. In addition to the human genome, we are seeing the emergence of other “omic” data (e.g., transcriptomics, epigenomics, and proteomics) in epidemiologic research. Identifying gene-environment interactions can help us identify new or confirm suspected environmental risk factors for disease; aid our understanding of disease natural history, severity and heterogeneity; and stratify disease risks and differentiate interventions for different subgroups of the population.

To explore work on gene-environment interaction (GxE) at the Centers for Disease Control and Prevention (CDC) and the Agency for Toxic Substances and Disease Registry (ATSDR), we examined the CDC-Authored Genomics and Precision Health Publications Database (CDC-Authored GPHPD), which includes articles published by CDC/ATSDR authors since 2011. The goal of our search was to identify publications describing the role of specific genes, gene signatures, or molecular pathways and their effects in response to environmental exposures. We defined environment broadly, including infectious agents, toxins, and behavioral risk factors such as alcohol use and smoking. We included articles examining various aspects of gene sequence, expression, and function, including sequence variants, gene-gene interaction, single nucleotide polymorphisms, DNA methylation, molecular methods of cellular function and damage, molecular and cellular signaling pathways, epigenetics, and telomere length. Genetic changes in microbes, animal vectors, and humans were included. Research applying genomic methods to develop treatments or vaccines, to understand antimicrobial mechanisms of resistance, and to examine evolutionary processes were also included.

The CDC-Authored GPHPD was searched using the terms “environment,” “gene environment,” “gene environment interaction,” and others* returning 54 unique articles, of which 15 were excluded because their primary focus was on other topics. Overall, these 39 articles represent 1% of all CDC/ATSDR-authored publications in the database. More than half (23 of 39) of the articles represent epidemiologic studies including candidate gene and genome-wide association studies (GWAS) examining genetic effect modification on disease risk.

Reference information for the 39 papers is provided in the accompanying table.

The articles included a wide range of health outcomes, including birth defects, cancer, and cardiovascular, pulmonary, hepatic, immunologic, and neurologic diseases. The largest subset of articles (22/39) examined the effects of toxic exposures or toxicogenomic effects of chemicals, such as polychlorinated biphenyls, dioxins, heavy metals, and organic solvents. Occupational exposures involving crystalline silica and multiwalled carbon nanotubes were also studied in relation to genetic damage and initiation of disease processes. The next largest category (6 articles) included papers describing evolutionary selection pressures on infectious organisms, either in the natural environment or in host species. The development of treatments and vaccines (5 articles), methods and models for evaluating GxE (5 articles), and recommendations for future research (1 article) complete the remaining topics explored in these publications. Publications originated in 9 of the 16 national Centers or Offices of CDC. The National Institute of Occupational Safety and Health (NIOSH) and the National Center for Emerging Zoonotic and Infectious Disease (NCEZID) contributed the most with 12 and 8 articles, respectively.

In this review, we identified articles aligning with the traditional epidemiologic concept of GxE, as well as several associated with newer biomarkers of exposure, such as DNA methylation (epigenetics) and telomere length. We found some articles related to environmental interactions with inherited genotype and others on environmental exposures that damage genetic material and initiate molecular pathways of pathogenesis.

The relatively small number of CDC/ATSDR GxE publications highlight opportunities to expand GxE research in areas not yet represented in the CDC/ATSDR-authored literature. Expanding GxE research could explore the multifaceted nature of the complex relationships and interactions between genes, the environment, and health.

Additional benefits could be reaped by promoting collaborative research among CDC/ATSDR programs and with academic partners. For example, the National Health and Nutrition Examination Survey (NHANES) Biospecimen Program collects and stores DNA samples; however, none of the publications in this CDC/ATSDR-authored literature review presented work utilizing this resource. Evidence related to genotoxicity is evaluated and presented for more than 200 hazardous substances in ATSDR Toxicological Profiles. Similarly, collaborations with the Geospatial Research, Analysis and Services Program (GRASP) may offer other unique opportunities to advance GxE research through the application of geostatistical and temporal methods to visualize and evaluate the impact of, and relationships among, place and human, animal, and pathogen genomes. Such partnerships could provide opportunities to leverage both expertise and resources.

*Search conducted 9/11/2021. Additional search terms: alcohol, chemical, exposure, hazard, hazardous, host response, human genome, human genome and chemical, interaction, particulate matter, pollution, smoking, toxicity, and VOC. We recognize that articles focusing on other, specific environmental exposures could have been missed by limiting our search to these terms.





[1] Url: https://blogs.cdc.gov/genomics/2021/10/18/the-science-of-gene-environment/

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