Epigenetic studies in AD and Other Conditions

It is well-established that DNA methylation plays an important role in control of gene expression, which in turn can influence phenotypic variance and susceptibility to disease.

Dr. Ertekin-Taner's team hypothesizes that gene expression changes in the brain play a central role in susceptibility for Alzheimer's disease (AD); the lab has significant publications in support of this hypothesis. The assumption is that identification of specific methylation changes that underlie these gene expression changes will lead to identifying novel genes and pathways that are excellent druggable targets for AD.

The lab previously performed a gene expression genome-wide association study (GWAS) that assessed mRNA levels of approximately 24,000 transcripts in two brain regions (temporal cortex and cerebellum) for approximately 200 AD subjects and approximately 200 subjects with other pathologies (non-AD). A collection of CpG methylation data (methylome) for 92 of these same subjects (46 AD and 46 non-AD) was established using DNA isolated from the temporal cortex to evaluate the influence of DNA methylation on gene expression in the brain.

Specifically the data is being analyzed to:

  • Determine differentially methylated regions, such as comparing subjects with AD versus without AD to identify genes with altered methylation patterns in the brains of AD subjects
  • Evaluate gene promoter regions for strong correlations with gene expression to identify genes that are under strong epigenetic control in the human brain that may be relevant to disease

The lab has collected DNA methylation data for approximately 2 million CpGs and generated summary methylation phenotypes for approximately 12,000 unique gene promoters for correlation analysis with gene expression levels.

The analysis has identified significant correlations between promoter CpG methylation and gene expression levels for genes that are differentially expressed between subjects with and without AD and provides a list of interesting genes for further study.