Dataset Information

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

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.

SUBMITTER: Gardner OK

PROVIDER: S-EPMC6737295 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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

Gardner Olivia K OK Wang Lily L Van Booven Derek D Whitehead Patrice L PL Hamilton-Nelson Kara L KL Adams Larry D LD Starks Takiyah D TD Hofmann Natalia K NK Vance Jeffery M JM Cuccaro Michael L ML Martin Eden R ER Byrd Goldie S GS Haines Jonathan L JL Bush William S WS Beecham Gary W GW Pericak-Vance Margaret A MA Griswold Anthony J AJ

Human molecular genetics 20190901 18

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 seq ...[more]

PMID: 31162550

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Dataset Information

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

Publications

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

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