{"doi":"10.1101/2021.03.05.21252993","title":"Development and application of an evidence-based directed acyclic graph to evaluate the associations between metal mixtures and cardiometabolic outcomes","abstract":"Abstract Objectives Specifying analytic 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 diagraming metal mixture exposure and cardiometabolic outcomes. Methods We conducted a systematic literature search to develop the directed acyclic graph (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 compared the proportion of statements supported by the data to the proportion of conditional independence statements supported by 100 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 in the SLVDS and applied them using Bayesian kernel machine regression models. Results From the 42 articles included in the review, we developed an evidence-based DAG with 163 testable conditional independence statements (64% supported by SLVDS data). Only 5% of DAGs with randomly permuted nodes indicated more agreement with the data than our evidence-based DAG. We did not observe evidence for an association between metal mixtures and cardiometabolic outcomes in the pilot analysis. Conclusions We developed, tested, and applied an evidence-based approach to analyze associations between metal mixtures and cardiometabolic health.","journal":"medRxiv","year":2021,"id":217229,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9391,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":526677,"name":"Rachel Melamed","orcid":"0000-0003-3089-9806","position":1,"is_corresponding":false},{"id":401684,"name":"Katherine A. James","orcid":"0000-0001-5119-398X","position":2,"is_corresponding":false},{"id":247729,"name":"Tanya L. Alderete","orcid":"0000-0002-7751-9543","position":3,"is_corresponding":false},{"id":566233,"name":"Laura Corlin","orcid":"0000-0002-3348-9063","position":4,"is_corresponding":false},{"id":766650,"name":"Emily Riseberg","orcid":"0000-0003-4024-2533","position":0,"is_corresponding":true}],"reference_count":95,"raw_metadata":null,"created_at":"2026-07-18T23:53:20.374789Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}