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West Nile virus (WNV), a flavivirus transmitted by mosquito bites, causes primarily mild symptoms but can also be fatal. Therefore, predicting and controlling the spread of West Nile virus is essential for public health in endemic areas. We hypothesized that socioeconomic factors may influence human risk from WNV. We analyzed a list of weather, land use, mosquito surveillance, and socioeconomic variables for predicting WNV cases in 1-km hexagonal grids across the Chicago metropolitan area. We used a two-stage lightGBM approach to perform the analysis and found that hexagons with incomes above and below the median are influenced by the same top characteristics. We found that weather factors and mosquito infection rates were the strongest common factors. Land use and socioeconomic variables had relatively small contributions in predicting WNV cases. The Light GBM handles unbalanced data sets well and provides meaningful predictions of the risk of epidemic disease outbreaks.