Nat. Genet. 54, 4–17 (2022)
Microglia have a key role in brain pathologies and aging; however, to relate genetic risk of neurological and psychiatric disorders to alterations in microglial function specifically requires comprehensive transcriptome studies. A study in Nature Genetics provides a brain-wide human Microglia Genomic Atlas (MiGA) across disease pathologies and ages. de Paiva Lopes et al. used autopsy tissue from 100 individuals to analyze 255 primary human microglial samples from multiple brain regions. The authors mapped both expression and splicing quantitative trait loci and showed that a range of neurological disease susceptibility loci are associated with gene expression or splicing in microglia specifically. Fine mapping of these loci revealed potential causal variants that are located within microglia-specific enhancers, including those associated with the expression of P2RY12 (purinergic receptor) for Parkinson’s disease and USP6NL (a GTPase-activating protein) for Alzheimer’s disease. Although the mechanistic hypotheses resulting from this work require further investigation, the atlas presented provides a powerful platform upon which future studies can build.
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