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

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 the Comparative Toxicogenomics Database for 1,008 chemicals and nine dementia-related pathways (e.g., Alzheimer's disease, tauopathies). We tested pairwise chemical-dementia gene enrichment using Fisher's exact tests and proportional reporting ratios (PRR), accounting for multiple comparisons with false discovery rate (FDR<1×10-6).

RESULTS

Of 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 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.