Combining large-scale genome-wide survival analysis with endophenotypic association analysis, Huang et al. found that lower SPI1 expression may reduce the risk of AD by attenuating pro-inflammatory microglia; Specifically, SPI1 encodes a transcription factor PU.1 that is critical for microglial development, and the expression level of PU.1 regulates microglial functions, including proliferation, survival, and differentiation (Huang et al., 2017). Here, SPI1 is linked to Alzheimer disease.