An Alzheimer’s disease-associated common regulatory variant in a PTK2B intron alters microglial function

expression. Nonetheless, this variant affects both the transcriptome and phenotype of the cells: interferon gamma-responsive genes are downregulated, secreted chemokine levels are reduced, and microglial chemotaxis is affected. We propose the variant acts by altering microglial reactivity, consistent with the established role of these cells in AD progression. This work demonstrates the power of isogenic hiPSC models for functionally validating GWAS-identified common regulatory variants.