title: Integrated copy number and gene expression analysis detects a CREB1 association with Alzheimer's disease.
abstract: 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.
authors.affiliation: Department of Neurology, Alzheimer's Disease and Memory Disorders Center, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: C A
authors.initials: CA
authors.lastname: Shaw
authors.forename: I
authors.initials: I
authors.lastname: Sheffer
authors.forename: N
authors.initials: N
authors.lastname: Sule
authors.forename: S Z
authors.initials: SZ
authors.lastname: Powell
authors.forename: B
authors.initials: B
authors.lastname: Dawson
authors.forename: S N Y
authors.initials: SN
authors.lastname: Zaidi
authors.forename: K L
authors.initials: KL
authors.lastname: Bucasas
authors.forename: J R
authors.initials: JR
authors.lastname: Lupski
authors.forename: K C
authors.initials: KC
authors.lastname: Wilhelmsen
authors.forename: R
authors.initials: R
authors.lastname: Doody
authors.forename: K
authors.initials: K
authors.lastname: Szigeti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics* / Q000378:metabolism; D056915:DNA Copy Number Variations; D005136:Eye Proteins / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins