title: Variation in the dysbindin gene and normal cognitive function in three independent population samples.
abstract: The association between DTNBP1 genotype and cognitive abilities was investigated in three population samples (1054 Scottish, 1806 Australian and 745 English) of varying age. There was evidence in each of the cohorts for association (P < 0.05) to single nucleotide polymorphisms (SNPs) and haplotypes previously shown to relate to cognition. By comparison with previous findings, these associations included measures of memory, and there was at best equivocal evidence of association with general cognitive ability. Of the SNPs typed in all three cohorts, rs2619528 and rs1011313 showed significant association with measures of executive function in two cohorts, rs1018381 showed significant association with verbal ability in one cohort and rs2619522 showed significance/marginal significance with tests of memory, speed and executive function in two cohorts. For all these SNPs, the direction and magnitude of the allelic effects were consistent between cohorts and with previous findings. In the English cohort, a previously untested SNP (rs742105) located in a distinct haplotype block upstream of the other SNPs showed the strongest significance (P < 0.01) for measures of memory but weaker significance for general cognitive ability. Our results therefore support involvement of the dysbindin gene in cognitive function, but further work is needed to clarify the specific functional variants involved and the cognitive abilities with which they are associated.
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, UK. michelle.luciano@ed.ac.uk
authors.forename: M
authors.initials: M
authors.lastname: Luciano
authors.forename: F
authors.initials: F
authors.lastname: Miyajima
authors.forename: P A
authors.initials: PA
authors.lastname: Lind
authors.forename: T C
authors.initials: TC
authors.lastname: Bates
authors.forename: M
authors.initials: M
authors.lastname: Horan
authors.forename: S E
authors.initials: SE
authors.lastname: Harris
authors.forename: M J
authors.initials: MJ
authors.lastname: Wright
authors.forename: W E
authors.initials: WE
authors.lastname: Ollier
authors.forename: C
authors.initials: C
authors.lastname: Hayward
authors.forename: N
authors.initials: N
authors.lastname: Pendleton
authors.forename: A J
authors.initials: AJ
authors.lastname: Gow
authors.forename: P M
authors.initials: PM
authors.lastname: Visscher
authors.forename: J M
authors.initials: JM
authors.lastname: Starr
authors.forename: I J
authors.initials: IJ
authors.lastname: Deary
authors.forename: N G
authors.initials: NG
authors.lastname: Martin
authors.forename: A
authors.initials: A
authors.lastname: Payton
mesh_terms: D000368:Aged; D000483:Alleles; D001315:Australia; D002352:Carrier Proteins / Q000235:genetics*; D003071:Cognition / Q000502:physiology*; D015331:Cohort Studies; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D004739:England; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008568:Memory; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D011153:Population; D011597:Psychomotor Performance / Q000502:physiology; D012606:Scotland
chemical_list: D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins