Fig. 1: Analysis strategy.
From: Integrated genomic analysis and CRISPRi implicates EGFR in Alzheimer’s disease risk
Our post-GWAS framework consists of the following steps: “Preprocessing,” “Characterization,” “In silico validation,” and “Functional validation.” Genome-wide significant variants from Bellenguez et al.5 were leveraged to identify regions of interest. Putative causal variants were analyzed for functional contexts and linked to potential causal genes using enhancers, eQTL data, and TFBS predictions. These variant-to-gene (V2G) pairs were characterized in brain tissues and cell types. Independent assays, including enhancer–promoter interactions (EPI), QTLs, and open chromatin regions from new data sources, were used for in silico validation. Functional validation included promoter-focused Capture C, ATAC-seq, RNA-seq, and CRISPRi in microglial cells.
