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Gene expression and chromatin accessibility comparison in iPSC-derived microglia in African, European, and Amerindian genomes in Alzheimer's patients and controls.

Moura, S.; Nasciben, L. B.; Ramirez, A. M.; Coombs, L.; Rivero, J.; Van Booven, D. J.; DeRosa, B. A.; Hamilton-Nelson, K. L.; Whitehead, P. L.; Adams, L. D.; Starks, T. D.; Mena, P. R.; Illanes-Manrique, M.; Tejada, S.; Byrd, G. S.; Cornejo-Olivas, M. R.; Feliciano-Astacio, B. E.; Nuytemans, K.; Wang, L.; Pericak-Vance, M. A.; Dykxhoorn, D. M.; Rajabli, F.; Griswold, A. J.; Young, J. I.; Vance, J. M.

2024-08-27 genomics
10.1101/2024.08.27.609943 bioRxiv
Show abstract

Alzheimers disease (AD) risk differs between population groups, with African Americans and Hispanics being the most affected groups compared to non-Hispanic Whites. Genetic factors contribute significant risk to AD, but the genetic regulatory architectures (GRA) have primarily been studied in Europeans. Many AD genes are expressed in microglia; thus, we explored the impact of genetic ancestry (Amerindian (AI), African (AF), and European (EU)) on the GRA in iPSC-derived microglia from 13 individuals ([~]4 each with high global ancestry, AD and controls) through ATAC-seq and RNA-seq analyses. We identified several differentially accessible and expressed genes (2 and 10 AD-related, respectively) between ancestry groups. We also found a high correlation between the transcriptomes of iPSC-derived and brain microglia, supporting their use in human studies. This study provides valuable insights into genetically diverse microglia beyond the analysis of AD.

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