Alzheimer disease (AD) specific transcription, DNA methylation and splicing in twenty AD associated loci

Crystal Humphries, Martin A. Kohli, Patrice Whitehead, Deborah C. Mash, Margaret A. Pericak-Vance, John Gilbert

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Genome-wide association studies have identified twenty loci associated with late-onset Alzheimer disease (LOAD). We examined each of the twenty loci, specifically the ±. 50. kb region surrounding the most strongly associated variant, for changes in gene(s) transcription specific to LOAD. Post-mortem human brain samples were examined for expression, methylation, and splicing differences. LOAD specific differences were detected by comparing LOAD to normal and "disease" controls. Eight loci, prominently ABCA7, contain LOAD specific differences. Significant changes in the CELF1 and ZCWPW1 loci occurred in genes not located nearest the associated variant, suggesting that these genes should be investigated further as LOAD candidates.

Original languageEnglish (US)
Pages (from-to)37-45
Number of pages9
JournalMolecular and Cellular Neuroscience
Volume67
DOIs
StatePublished - Jul 1 2015

Keywords

  • DNA methylation
  • Dementia with Lewy bodies
  • Differential expression
  • Genome-wide association study
  • Late-onset Alzheimer disease
  • Microarray
  • RNA-Seq
  • Splicing
  • Transcription

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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