Genetic studies have associated thousands of non-coding variants with Alzheimer’s disease (AD), yet the functions of these variants remain elusive. We conducted cell-type-specific genetic fine mapping of AD variants and performed extensive functional characterization to unravel the causal variants that contribute to transcriptional regulation and ADrelated phenotypes in microglia.
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Nott, A. et al. Brain cell type-specific enhancer- promoter interactome maps and disease-risk association. Science 366, 1134–1139 (2019). This paper reports enrichment of AD variants at microglia enhancers.
Douvaras, P. et al. Directed differentiation of human pluripotent stem cells to microglia. Stem Cell Rep. 8, 1516–1524 (2017). This paper reports a method for differentiating hPSCs into microglia.
Bellenguez, C. et al. New insights into the genetic etiology of Alzheimer’s disease and related dementias. Nat. Genet. 54, 412–436 (2022). This paper presents the most comprehensive study of the AD genetic landscape.
Anzalone, A. V. et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature 576, 149–157 (2019). This paper describes prime-editing methods.
Ren, X. et al. High throughput PRIME editing screens identify functional DNA variants in the human genome. bioRxiv 2023.07.12.548736 (2021). This paper presents a high-throughput prime-editing method for characterizing genome function.
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This is a summary of: Yang, X. et al. Functional characterization of Alzheimer’s disease genetic variants in microglia. Nat. Genet. https://doi.org/10.1038/s41588-023-01506-8 (2023).
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Linking non-coding variants to function in microglia in Alzheimer’s disease. Nat Genet 55, 1615–1616 (2023). https://doi.org/10.1038/s41588-023-01503-x