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A Data Mining Approach Reveals Chemicals Detected at Higher Levels in Non-Hispanic Black Women Target Preterm Birth Genes and Pathways

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Abstract

Preterm birth occurs disproportionately in the USA non-Hispanic Black population. Black women also face disproportionate exposure to certain environmental chemicals. The goal of this study was to use publicly available toxicogenomic data to identify chemical exposures that may contribute to preterm birth disparities. We tested 19 chemicals observed at higher levels in the blood or urine of non-Hispanic Black women compared to non-Hispanic White women. We obtained chemical-gene interactions from the Comparative Toxicogenomics Database and a list of genes involved in preterm birth from the Preterm Birth Database. We tested chemicals for enrichment with preterm birth genes using chi-squared tests. We then conducted pathway enrichment analysis for the preterm birth genes using DAVID software and identified chemical impacts on genes involved in these pathways. Genes annotated to all 19 chemicals were enriched with preterm birth genes (FDR-adjusted p value < 0.05). Preterm birth enriched chemicals that were detected at the highest levels in non-Hispanic Black women included methyl mercury, methylparaben, propylparaben, diethyl phthalate, dichlorodiphenyldichloroethylene, and bisphenol S. The preterm birth genes were enriched for pathways including “inflammatory response” (FDR-adjusted p value = 3 × 10–19), “aging” (FDR-adjusted p value = 4 × 10–8) and “response to estradiol” (FDR-adjusted p value = 2 × 10–4). Chemicals enriched with preterm birth genes impacted genes in all three pathways. This study adds to the body of knowledge suggesting that exposures to environmental chemicals contribute to racial disparities in preterm birth and that multiple chemicals drive these effects. These chemicals affect genes involved in biological processes relevant to preterm birth such as inflammation, aging, and estradiol pathways.

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Data Availability

Not applicable.

Code Availability

The R markdown code used to conduct these analyses and generate figures is available at https://github.com/bakulskilab.

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Funding

This research was supported by the Michigan Center on Lifestage Environmental Exposures and Disease (P30ES017885). Drs. Harris, Bakulski and Loch-Caruso were supported by the National Institute of Environmental Health Sciences of the National Institutes of Health under Award Number P42ES017198. Additional funding for Dr. Harris was provided by the National Center for Advancing Translational Sciences (UL1TR002240). Dr. Bakulski was supported by grants from the National Institutes of Health (R01ES025531; R01ES025574; R01AG055406; R01MD013299). Dr. Colacino and Dr. Nguyen were supported by grants from the National Institutes of Health (R01ES028802 and R01ES028802S1). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA

    Sean M. Harris, Justin Colacino, Vy Nguyen & Rita Loch-Caruso

  2. Department of Nutritional Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA

    Justin Colacino

  3. Center for Computational Medicine and Bioinformatics, Medical School, University of Michigan, Ann Arbor, MI, USA

    Justin Colacino

  4. Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA

    Miatta Buxton & Kelly M. Bakulski

  5. College of Literature, Science and the Arts, University of Michigan, Ann Arbor, MI, USA

    Lauren Croxton

  6. Department of Computational Medicine and Bioinformatics, Medical School, University of Michigan, Ann Arbor, MI, USA

    Vy Nguyen

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  1. Sean M. Harris
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Harris, S.M., Colacino, J., Buxton, M. et al. A Data Mining Approach Reveals Chemicals Detected at Higher Levels in Non-Hispanic Black Women Target Preterm Birth Genes and Pathways. Reprod. Sci. 29, 2001–2012 (2022). https://doi.org/10.1007/s43032-022-00870-w

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