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

Sofia Moura; Luciana Bertholim Nasciben; Aura María Ramírez; Lauren E. Coombs; Joe Rivero; Derek J. Van Booven; Brooke A. DeRosa; Kara L. Hamilton‐Nelson; Patrice L. Whitehead; Larry Deon Adams; Takiyah D. Starks; Pedro Ramon Mena; Maryenela Illanes‐Manrique; Sergio J. Tejada; Goldie S. Byrd; Mario Cornejo‐Olivas; Briseida E. Feliciano‐Astacio; Karen Nuytemans; Liyong Wang; Margaret Ann Pericak‐Vance; Derek Michael Dykxhoorn; Farid Rajabli; Anthony J. Griswold; Juan I. Young; Jeffery M. Vance

doi:10.1101/2024.08.27.609943

GenomicsbioRxivAug 27, 2024

Preprint

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

Sofia Moura iD, Luciana Bertholim Nasciben iD, Aura María Ramírez iD, Lauren E. Coombs, Joe Rivero, Derek J. Van Booven iD, Brooke A. DeRosa iD, Kara L. Hamilton‐Nelson iD, Patrice L. Whitehead, Larry Deon Adams, Takiyah D. Starks iD, Pedro Ramon Mena iD, Maryenela Illanes‐Manrique iD, Sergio J. Tejada, Goldie S. Byrd iD, Mario Cornejo‐Olivas iD, Briseida E. Feliciano‐Astacio iD, Karen Nuytemans iD, Liyong Wang iD, Margaret Ann Pericak‐Vance iD, Derek Michael Dykxhoorn iD, Farid Rajabli iD, Anthony J. Griswold iD, Juan I. Young iD, Jeffery M. Vance iD

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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