Exposome and Exposure Modeling

Sponsors

National Institute of Health

People

Vy Nguyen (nguyenvy@umich.edu)

Sarah Brabec (sbrabec@umich.edu)

Adam Kahana (kahanaa@umich.edu)

Julien Heidt (julienh@umich.edu)

Katelyn Polemi (kmpolemi@umich.edu)

Jacob Kvasnicka (jkvas@umich.edu)

Jon Arnot (jon@arnotresearch.com)

Justin Colacino (colacino@umich.edu)

Chirag Patel (Chirag_Patel@hms.harvard.edu)

Olivier Jolliet (ojolliet@umich.edu)

Keywords

Exposome, big data, environmental chemicals, biomonitoring, age-based exposures, temporal trends, racial disparities, occupational exposures, physiological dysfunction

A New Visualization Tool to Identify Chemical Exposure Disparities by Demographic Traits

Variations in chemical exposure by demographic traits have been well studied individually for specific chemical classes but are not systematically studied for a wide range of chemicals to contrast the influence of demographic traits on chemical exposure patterns. This study aims to develop a new analysis and visualization tool that enables us to analyze and compare exposure patterns for a large number of traits and a broad set of 229 chemicals in the US population. We conducted a series of multiple regression models with the chemical biomarker levels as the outcome variable and the main predictors as age, sex, ethnicity, smoking behaviors, and poverty income ratio while adjusting for urinary flow and study years. We developed a visualization tool known as the Alphabet Soup Plot that displays the magnitude of associations between each chemical biomarker and each inherent trait. We identified widespread differences in chemical biomarker levels by different populations. Development of this visualization tool enables us to comprehensively quantify the influence of several inherent traits on multiple chemical exposure patterns and to identify which combination of chemicals and populations should be prioritized for further toxicological evaluation and targeted health interventions.

A Comprehensive Analysis of Racial Disparities in Chemical Exposure Biomarkers in US Women

African American women are 2 to 3 times more likely to be diagnosed with triple negative breast cancer, relative to European American women. While health disparities are likely due to complex interactions between genetic, social, and lifestyle factors, the impact of genetic factors on disease disparities appears to be minor, but the impact of environmental exposures may be substantially higher. To better understand environmental factors which may impact triple negative breast cancer risk, we sought to comprehensively quantify differences in environmental exposures for 148 chemicals in US women by race. To identify differences in chemical biomarker concentrations chemicals by race, we ran survey weighted linear regressions of chemical concentrations in participants, adjusting for age, race/ethnicity, poverty-income ratio, cotinine level, and the cycles (years) in which the participants were sampled. Results were then stratified by race/ethnicity and by age groups (0-11, 12-25, 26-50, 51-up). Body burdens of chemicals are substantially different by race in a representative sample of US women. Many of the chemicals with exposure disparities are found in cosmetics and other consumer products. To better understand the link between the environment and triple negative breast cancer disparities, ongoing work is conducting experiments driven by the results of this study to determine whether these toxicants impact biological pathways associated with breast cancer.

Biomarker Based Occupational Exposome

Occupational exposures are thought to be responsible for over 370,000 premature deaths each year. Thus, the precise quantification of occupational exposure is necessary to consider in understanding an individual’s exposome, the entirety of chemical exposures in a lifetime. We systematically contrast occupational exposures between blue collar and white collar workers across a variety of industrial sectors as well as characterize differences in physiological dysfunction in this population by implementing a series of regression models. Systematically studying the NHANES chemical biomarkers and occupational datasets by implementing an untargeted approach enables the identification of workers who are at risk to high exposures and consequentially adverse health outcomes. These findings can be utilized to prioritize chemicals and workers for toxicological evaluation or health interventions.

Biomarker-Based Assessment of the Influence of Chemical Exposures on Chronic Kidney Disease

Chronic Kidney Disease (CKD) was the 9th leading cause of death in the United States in 2015. Previous studies have identified environmental toxicants such as Per- and polyfluoroalkyl substances and heavy metals to be associated with CKD but focused on only a handful of chemical classes corresponding with a few biomarkers of CKD. To better understand the influence of environmental toxicants on CKD, we implemented an overarching screening approach to systematically evaluate the associations between 167 chemical biomarkers and 4 biomarkers of CKD (Cystatin, Glomerular Filtration Rate, Albumin, and Creatinine) as well as identify populations at risk for CKD.

Exposome-Wide Association Study on Physiological Stress Response

Physiological stress response can be characterized by measurements of various health biomarkers, which represent various biological pathways including inflammation, metabolic syndrome, and primary stress response, and can be integrated into a total allostatic load to represent the burden of chronic stress. This score has been shown to be associated with a few heavy metals such as lead and cadmium but focus on only a few chemical chemicals for a few physiological indictors. To better understand the influence of environmental toxicants on perturbing a participant’s physiology, we will implement an overarching screening approach to systematically evaluate the associations between 411 chemical biomarkers and 41 biomarkers of physiological stress responses to identify populations at risk for chemical-mediated adverse health outcomes.

Publications

Peer-reviewed journal articles

1. Nguyen, Vy Kim, et al. "Characterization of age-based trends to identify chemical biomarkers of higher levels in children." Environment international 122 (2019): 117-129.