Alzheimer disease (AD) specific transcription, DNA methylation and splicing in twenty AD associated loci
Molecular and Cellular Neuroscience(2015)
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 ±50kb 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.
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Key words
Late-onset Alzheimer disease,Genome-wide association study,Transcription,Differential expression,RNA-Seq,Microarray,DNA methylation,Splicing,Dementia with Lewy bodies
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