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

IntroductionDementia 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. MethodsWe obtained gene lists from the Comparative Toxicogenomics Database for 1,008 chemicals and nine dementia-related pathways (e.g., Alzheimers disease, tauopathies). We tested pairwise chemical-dementia gene enrichment using Fishers exact tests and proportional reporting ratios (PRR), accounting for multiple comparisons with false discovery rate (FDR<1x10-6). ResultsOf the chemicals tested, 742 (73.6%) were enriched for at least one dementia pathway and 15 with all nine pathways, including benzo(a)pyrene, ethanol, paraquat, and particulate matter. We observed 295 chemicals enriched for Alzheimers disease, including sodium arsenite (PRR = 57.9) and 305 enriched for tauopathies, including bisphenol A (PRR=37.7). DiscussionWe identified chemicals enriched for dementia pathways, suggesting broad classes of chemicals contribute to dementia.