title: Calmodulin-binding transcription activator 1 (CAMTA1) alleles predispose human episodic memory performance.
abstract: Little is known about the genes and proteins involved in the process of human memory. To identify genetic factors related to human episodic memory performance, we conducted an ultra-high-density genome-wide screen at > 500 000 single nucleotide polymorphisms (SNPs) in a sample of normal young adults stratified for performance on an episodic recall memory test. Analysis of this data identified SNPs within the calmodulin-binding transcription activator 1 (CAMTA1) gene that were significantly associated with memory performance. A follow up study, focused on the CAMTA1 locus in an independent cohort consisting of cognitively normal young adults, singled out SNP rs4908449 with a P-value of 0.0002 as the most significant associated SNP in the region. These validated genetic findings were further supported by the identification of CAMTA1 transcript enrichment in memory-related human brain regions and through a functional magnetic resonance imaging experiment on individuals matched for memory performance that identified CAMTA1 allele-specific upregulation of medial temporal lobe brain activity in those individuals harboring the 'at-risk' allele for poorer memory performance. The CAMTA1 locus encodes a purported transcription factor that interfaces with the calcium-calmodulin system of the cell to alter gene expression patterns. Our validated genomic and functional biological findings described herein suggest a role for CAMTA1 in human episodic memory.
authors.affiliation: Neurogenomics Division, The Translational Genomics Research Institute, 445 N Fifth Street, Phoenix, AZ 85004, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Huentelman
authors.forename: Andreas
authors.initials: A
authors.lastname: Papassotiropoulos
authors.forename: David W
authors.initials: DW
authors.lastname: Craig
authors.forename: Frederic J
authors.initials: FJ
authors.lastname: Hoerndli
authors.forename: John V
authors.initials: JV
authors.lastname: Pearson
authors.forename: Kim-Dung
authors.initials: KD
authors.lastname: Huynh
authors.forename: Jason
authors.initials: J
authors.lastname: Corneveaux
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hänggi
authors.forename: Christian R A
authors.initials: CR
authors.lastname: Mondadori
authors.forename: Andreas
authors.initials: A
authors.lastname: Buchmann
authors.forename: Eric M
authors.initials: EM
authors.lastname: Reiman
authors.forename: Katharina
authors.initials: K
authors.lastname: Henke
authors.forename: Dominique J-F
authors.initials: DJ
authors.lastname: de Quervain
authors.forename: Dietrich A
authors.initials: DA
authors.lastname: Stephan
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D016678:Genome; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory; D011939:Mental Recall / Q000502:physiology; D051379:Mice; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism
chemical_list: C487554:CAMTA1 protein, human; D002135:Calcium-Binding Proteins; D015534:Trans-Activators