Discussion
This resource will be valuable in evaluating AD in admixed populations and other neurological disorders and understanding the AD risk differences between populations. Highlights: First comparison of the genomics of AI, AF, and EU microglia. Report differences in expression and accessibility of AD genes between ancestries. Ancestral expression differences are greater than differences in accessibility. Good transcriptome correlation was seen between brain and iPSC-derived microglia. Differentially expressed AD genes were in known AD pathways.
Methods
We created iPSC-derived microglia from 13 individuals of either high Amerindian (AI), African (AF), or EU global ancestry, including both AD and controls. RNA-seq, ATAC-seq, and pathway analyses were compared between ancestries in both AD and non-AD genes.
Results
Twelve AD genes were differentially expressed genes (DEGs) and/or accessible between ancestries, including ABI3, CTSB, and MS4A6A. A total of 5% of all genes had differential ancestral expression, but differences in accessibility were less than 1%. The DEGs were enriched in known AD pathways.