RNA editing alterations in a multi-ethnic Alzheimer disease cohort converge on immune and endocytic molecular pathways

Olivia K. Gardner, Lily Wang, Derek Van Booven, Patrice L. Whitehead, Kara L. Hamilton-Nelson, Larry D. Adams, Takiyah D. Starks, Natalia K. Hofmann, Jeffery M Vance, Michael Cuccaro, Eden R Martin, Goldie S. Byrd, Jonathan L. Haines, William S. Bush, Gary W Beecham, Margaret A. Pericak-Vance, Anthony Griswold

Research output: Contribution to journalArticle

Abstract

Little is known about the post-transcriptional mechanisms that modulate the genetic effects in the molecular pathways underlying Alzheimer disease (AD), and even less is known about how these changes might differ across diverse populations. RNA editing, the process that alters individual bases of RNA, may contribute to AD pathogenesis due to its roles in neuronal development and immune regulation. Here, we pursued one of the first transcriptome-wide RNA editing studies in AD by examining RNA sequencing data from individuals of both African-American (AA) and non-Hispanic White (NHW) ethnicities. Whole transcriptome RNA sequencing and RNA editing analysis were performed on peripheral blood specimens from 216 AD cases (105 AA, 111 NHW) and 212 gender matched controls (105 AA, 107 NHW). 449 positions in 254 genes and 723 positions in 371 genes were differentially edited in AA and NHW, respectively. While most differentially edited sites localized to different genes in AA and NHW populations, these events converged on the same pathways across both ethnicities, especially endocytic and inflammatory response pathways. Furthermore, these differentially edited sites were preferentially predicted to disrupt miRNA binding and induce nonsynonymous coding changes in genes previously associated with AD in molecular studies, including PAFAH1B2 and HNRNPA1. These findings suggest RNA editing is an important post-transcriptional regulatory program in AD pathogenesis.

Original languageEnglish (US)
Pages (from-to)3053-3061
Number of pages9
JournalHuman molecular genetics
Volume28
Issue number18
DOIs
StatePublished - Sep 15 2019

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RNA Editing
Alzheimer Disease
African Americans
RNA Sequence Analysis
Transcriptome
Genes
Gene Order
MicroRNAs
Population
RNA

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

RNA editing alterations in a multi-ethnic Alzheimer disease cohort converge on immune and endocytic molecular pathways. / Gardner, Olivia K.; Wang, Lily; Van Booven, Derek; Whitehead, Patrice L.; Hamilton-Nelson, Kara L.; Adams, Larry D.; Starks, Takiyah D.; Hofmann, Natalia K.; Vance, Jeffery M; Cuccaro, Michael; Martin, Eden R; Byrd, Goldie S.; Haines, Jonathan L.; Bush, William S.; Beecham, Gary W; Pericak-Vance, Margaret A.; Griswold, Anthony.

In: Human molecular genetics, Vol. 28, No. 18, 15.09.2019, p. 3053-3061.

Research output: Contribution to journalArticle

Gardner, OK, Wang, L, Van Booven, D, Whitehead, PL, Hamilton-Nelson, KL, Adams, LD, Starks, TD, Hofmann, NK, Vance, JM, Cuccaro, M, Martin, ER, Byrd, GS, Haines, JL, Bush, WS, Beecham, GW, Pericak-Vance, MA & Griswold, A 2019, 'RNA editing alterations in a multi-ethnic Alzheimer disease cohort converge on immune and endocytic molecular pathways', Human molecular genetics, vol. 28, no. 18, pp. 3053-3061. https://doi.org/10.1093/hmg/ddz110
Gardner OK, Wang L, Van Booven D, Whitehead PL, Hamilton-Nelson KL, Adams LD et al. RNA editing alterations in a multi-ethnic Alzheimer disease cohort converge on immune and endocytic molecular pathways. Human molecular genetics. 2019 Sep 15;28(18):3053-3061. https://doi.org/10.1093/hmg/ddz110
Gardner, Olivia K. ; Wang, Lily ; Van Booven, Derek ; Whitehead, Patrice L. ; Hamilton-Nelson, Kara L. ; Adams, Larry D. ; Starks, Takiyah D. ; Hofmann, Natalia K. ; Vance, Jeffery M ; Cuccaro, Michael ; Martin, Eden R ; Byrd, Goldie S. ; Haines, Jonathan L. ; Bush, William S. ; Beecham, Gary W ; Pericak-Vance, Margaret A. ; Griswold, Anthony. / RNA editing alterations in a multi-ethnic Alzheimer disease cohort converge on immune and endocytic molecular pathways. In: Human molecular genetics. 2019 ; Vol. 28, No. 18. pp. 3053-3061.
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