{Reference Type}: Journal Article {Title}: Exploring Climate-Disease Connections in Geopolitical Versus Ecological Regions: The Case of West Nile Virus in the United States. {Author}: Moser SK;Spencer JA;Barnard M;Hyman JM;Manore CA;Gorris ME; {Journal}: Geohealth {Volume}: 8 {Issue}: 6 {Year}: 2024 Jun {Factor}: 6.343 {DOI}: 10.1029/2024GH001024 {Abstract}: Many infectious disease forecasting models in the United States (US) are built with data partitioned into geopolitical regions centered on human activity as opposed to regions defined by natural ecosystems; although useful for data collection and intervention, this has the potential to mask biological relationships between the environment and disease. We explored this concept by analyzing the correlations between climate and West Nile virus (WNV) case data aggregated to geopolitical and ecological regions. We compared correlations between minimum, maximum, and mean annual temperature; precipitation; and annual WNV neuroinvasive disease (WNND) case data from 2005 to 2019 when partitioned into (a) climate regions defined by the National Oceanic and Atmospheric Administration (NOAA) and (b) Level I ecoregions defined by the Environmental Protection Agency (EPA). We found that correlations between climate and WNND in NOAA climate regions and EPA ecoregions were often contradictory in both direction and magnitude, with EPA ecoregions more often supporting previously established biological hypotheses and environmental dynamics underlying vector-borne disease transmission. Using ecological regions to examine the relationships between climate and disease cases can enhance the predictive power of forecasts at various scales, motivating a conceptual shift in large-scale analyses from geopolitical frameworks to more ecologically meaningful regions.