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Development and application of an evidence-based directed acyclic graph to evaluate the associations between metal mixtures and cardiometabolic outcomes

  • Emily Riseberg ORCID logo , Rachel D. Melamed ORCID logo , Katherine A. James ORCID logo , Tanya L. Alderete and Laura Corlin ORCID logo EMAIL logo
Published/Copyright: June 27, 2023
Become an author with De Gruyter Brill

Abstract

Objectives

Specifying causal models to assess relationships among metal mixtures and cardiometabolic outcomes requires evidence-based models of the causal structures; however, such models have not been previously published. The objective of this study was to develop and evaluate a directed acyclic graph (DAG) diagraming metal mixture exposure and cardiometabolic outcomes.

Methods

We conducted a literature search to develop the DAG of metal mixtures and cardiometabolic outcomes. To evaluate consistency of the DAG, we tested the suggested conditional independence statements using linear and logistic regression analyses with data from the San Luis Valley Diabetes Study (SLVDS; n=1795). We calculated the proportion of statements supported by the data and compared this to the proportion of conditional independence statements supported by 1,000 DAGs with the same structure but randomly permuted nodes. Next, we used our DAG to identify minimally sufficient adjustment sets needed to estimate the association between metal mixtures and cardiometabolic outcomes (i.e., cardiovascular disease, fasting glucose, and systolic blood pressure). We applied them to the SLVDS using Bayesian kernel machine regression, linear mixed effects, and Cox proportional hazards models.

Results

From the 42 articles included in the review, we developed an evidence-based DAG with 74 testable conditional independence statements (43 % supported by SLVDS data). We observed evidence for an association between As and Mn and fasting glucose.

Conclusions

We developed, tested, and applied an evidence-based approach to analyze associations between metal mixtures and cardiometabolic health.


Corresponding author: Laura Corlin, Department of Public Health and Community Medicine, Tufts University, 136 Harrison Avenue, Boston, MA 02111, USA; and Department of Civil and Environmental Engineering, Tufts University, Medford, MA, USA, E-mail:

All the intellectual property and data generated were administered according to policies from the University of Colorado and the NIH, including the NIH Data Sharing Policy and Implementation Guidance of March 5, 2003. The San Luis Valley Diabetes Study (SLVDS) summary data can be shared with the scientific community in accordance with the SLVDS data sharing plan (which includes Data Use Agreements and anonymizing of data to protect subject confidentiality). Analytic code is available upon reasonable request from the corresponding author.


Award Identifier / Grant number: R00ES027853

Funding source: Tufts Institute of the Environment

Funding source: Tufts University Department of Public Health and Community Medicine

Award Identifier / Grant number: K12HD092535

Acknowledgments

We would like to thank the participants and staff of the San Luis Valley Diabetes Study.

  1. Research funding: Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) grant number K12HD092535 (Corlin), Tufts University Department of Public Health and Community Medicine (Corlin and Riseberg), Tufts Institute of the Environment (Riseberg), R00ES027853 (Alderete).

  2. Author contribution: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The SLVDS was approved by the Colorado Multiple Institutional Review Board. The Tufts University Social, Behavioral & Educational Research Institutional Review Board deemed this study Not Human Subjects Research (study # 00000131).

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/em-2022-0133).


Received: 2022-08-30
Accepted: 2023-06-05
Published Online: 2023-06-27

© 2023 Walter de Gruyter GmbH, Berlin/Boston

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