Integrated copy number and gene expression analysis detects a CREB1 association with Alzheimer's disease

Transl Psychiatry. 2012 Nov 20;2(11):e192. doi: 10.1038/tp.2012.119.


Genetic variation, both single-nucleotide variations and copy number variations (CNV), contribute to changes in gene expression. In some cases these variations are meaningfully correlated with disease states. We hypothesized that in a genetically heterogeneous disorder such as sporadic Alzheimer's disease (AD), utilizing gene expression as a quantitative trait and CNVs as a genetic marker map within the same individuals in the context of case-control status may increase the power to detect relevant loci. Using this approach an 8-kb deletion was identified that contains a PAX6-binding site on chr2q33.3 upstream of CREB1 encoding the cAMP responsive element-binding protein1 transcription factor. The association of the CNV to AD was confirmed by a case-control association study consisting of the Texas Alzheimer Research and Care Consortium and NIA-LOAD Family Study data sets.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism
  • Case-Control Studies
  • Cyclic AMP Response Element-Binding Protein / genetics*
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • DNA Copy Number Variations
  • Eye Proteins / metabolism
  • Female
  • Gene Expression Profiling
  • Genetic Predisposition to Disease
  • Genotype
  • Homeodomain Proteins / metabolism
  • Humans
  • Male
  • Middle Aged
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors / metabolism
  • Repressor Proteins / metabolism


  • CREB1 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • Eye Proteins
  • Homeodomain Proteins
  • PAX6 Transcription Factor
  • PAX6 protein, human
  • Paired Box Transcription Factors
  • Repressor Proteins