title: Association of a nonsynonymous variant of DAOA with visuospatial ability in a bipolar family sample.
abstract: BACKGROUND
  Bipolar disorder and schizophrenia are hypothesized to share some genetic background.
  
  
  METHODS
  In a two-phase study, we evaluated the effect of five promising candidate genes for psychotic disorders, DAOA, COMT, DTNBP1, NRG1, and AKT1, on bipolar spectrum disorder, psychotic disorder, and related cognitive endophenotypes in a Finnish family-based sample ascertained for bipolar disorder.
  
  
  RESULTS
  In initial screening of 362 individuals from 63 families, we found only marginal evidence for association with the diagnosis-based dichotomous classification. Those associations did not strengthen when we genotyped the complete sample of 723 individuals from 180 families. We observed a significant association of DAOA variants rs3916966 and rs2391191 with visuospatial ability (Quantitative Transmission Disequilibrium Test [QTDT]; p = 4 x 10(-6) and 5 x 10(-6), respectively) (n = 159) with the two variants in almost complete linkage disequilibrium. The COMT variant rs165599 also associated with visuospatial ability, and in our dataset, we saw an additive effect of DAOA and COMT variants on this neuropsychological trait.
  
  
  CONCLUSIONS
  The ancestral allele (Arg) of the nonsynonymous common DAOA variant rs2391191 (Arg30Lys) was found to predispose to impaired performance. The DAOA gene may play a role in predisposing individuals to a mixed phenotype of psychosis and mania and to impairments in related neuropsychological traits.
authors.affiliation: Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland.
authors.forename: Pia
authors.initials: P
authors.lastname: Soronen
authors.forename: Kaisa
authors.initials: K
authors.lastname: Silander
authors.forename: Mervi
authors.initials: M
authors.lastname: Antila
authors.forename: Outi M
authors.initials: OM
authors.lastname: Palo
authors.forename: Annamari
authors.initials: A
authors.lastname: Tuulio-Henriksson
authors.forename: Tuula
authors.initials: T
authors.lastname: Kieseppä
authors.forename: Pekka
authors.initials: P
authors.lastname: Ellonen
authors.forename: Juho
authors.initials: J
authors.lastname: Wedenoja
authors.forename: Joni A
authors.initials: JA
authors.lastname: Turunen
authors.forename: Olli P H
authors.initials: OP
authors.lastname: Pietiläinen
authors.forename: William
authors.initials: W
authors.lastname: Hennah
authors.forename: Jouko
authors.initials: J
authors.lastname: Lönnqvist
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Timo
authors.initials: T
authors.lastname: Partonen
authors.forename: Tiina
authors.initials: T
authors.lastname: Paunio
mesh_terms: D000704:Analysis of Variance; D001714:Bipolar Disorder / Q000235:genetics* / Q000503:physiopathology*; D002352:Carrier Proteins / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015810:Linkage Disequilibrium; D008297:Male; D009483:Neuropsychological Tests; D010775:Photic Stimulation; D020641:Polymorphism, Single Nucleotide; D013028:Space Perception / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; C475071:DAOA protein, human; D047908:Intracellular Signaling Peptides and Proteins; D002394:Catechol O-Methyltransferase