Identification of chemicals targeting dementia genes and pathways in the Comparative Toxicogenomics Database

Abstract INTRODUCTION Dementia is a public health challenge and exposures likely contribute to risk, though many have not been evaluated. We screened chemicals for enrichment with dementia genes and related pathways. METHODS We obtained gene lists from Agora and the Comparative Toxicogenomics Database (CTD) for 1008 chemicals and nine dementia‐related pathways (e.g., Alzheimer's disease, tauopathies). We tested pairwise chemical–dementia gene enrichment using Fisher exact tests and proportional reporting ratios (PRRs), accounting for multiple comparisons with false discovery rate (FDR < 1 × 10 −6 ). RESULTS Of the chemicals tested, 817 (81.1%) were enriched for at least one dementia pathway and 71 with all nine pathways, including benzo(a)pyrene, ethanol, paraquat, and particulate matter. We observed 295 chemicals enriched for Alzheimer's disease, including sodium arsenite (PRR = 57.9) and 305 enriched for tauopathies, including bisphenol A (PRR = 37.7). DISCUSSION We identified chemicals enriched for dementia pathways, suggesting broad classes of chemicals contribute to dementia.