title: Association between Dopamine Receptor D2 (DRD2) Variations rs6277 and rs1800497 and Cognitive Performance According to Risk Type for Psychosis: A Nested Case Control Study in a Finnish Population Sample.
abstract: BACKGROUND
  There is limited research regarding the association between genes and cognitive intermediate phenotypes in those at risk for psychotic disorders.
  
  
  METHODS
  We measured the association between established psychosis risk variants in dopamine D2 receptor (DRD2) and cognitive performance in individuals at age 23 years and explored if associations between cognition and these variants differed according to the presence of familial or clinical risk for psychosis. The subjects of the Oulu Brain and Mind Study were drawn from the general population-based Northern Finland 1986 Birth Cohort (NFBC 1986). Using linear regression, we compared the associations between cognitive performance and two candidate DRD2 polymorphisms (rs6277 and rs1800497) between subjects having familial (n=61) and clinical (n=45) risk for psychosis and a random sample of participating NFBC 1986 controls (n=74). Cognitive performance was evaluated using a comprehensive battery of tests at follow-up.
  
  
  RESULTS
  Principal components factor analysis supported a three-factor model for cognitive measures. The minor allele of rs6277 was associated with poorer performance on a verbal factor (p=0.003) but this did not significantly interact with familial or clinical risk for psychosis. The minor allele of rs1800497 was associated with poorer performance on a psychomotor factor (p=0.038), though only in those at familial risk for psychotic disorders (interaction p=0.049).
  
  
  CONCLUSIONS
  The effect of two DRD2 SNPs on cognitive performance may differ according to risk type for psychosis, suggesting that cognitive intermediate phenotypes differ according to the type (familial or clinical) risk for psychosis.
authors.affiliation: Department of Psychiatry, Centre for Clinical Neuroscience, University of Oulu, Oulu, Finland; Health Service Executive, Dublin, Ireland.
authors.forename: Hugh
authors.initials: H
authors.lastname: Ramsay
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom; Cambridge Cognition Ltd., Bottisham, Cambridge, United Kingdom.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Barnett
authors.affiliation: Department of Psychiatry, Centre for Clinical Neuroscience, University of Oulu, Oulu, Finland; Institute of Health Sciences, University of Oulu, Oulu, Finland; Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland.
authors.forename: Jouko
authors.initials: J
authors.lastname: Miettunen
authors.affiliation: Department of Psychiatry, Oulu University Hospital, Oulu, Finland.
authors.forename: Sari
authors.initials: S
authors.lastname: Mukkala
authors.affiliation: Department of Psychiatry, Centre for Clinical Neuroscience, University of Oulu, Oulu, Finland; Department of Psychiatry, Oulu University Hospital, Oulu, Finland; Department of Psychiatry, Länsi-Pohja healthcare district, Finland; Department of Psychiatry, the Middle Ostrobothnia Central Hospital, Kiuru, Finland; Mental health services, Joint Municipal Authority of Wellbeing in Raahe District, Finland; Mental health services, Basic Health Care District of Kallio, Finland; Visala Hospital, the Northern Ostrobothnia Hospital District, Finland.
authors.forename: Pirjo
authors.initials: P
authors.lastname: Mäki
authors.affiliation: Public Health Genomics Unit, National Institute for Health and Welfare and Institute for Molecular Medicine, Helsinki, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Liuhanen
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.
authors.forename: Graham K
authors.initials: GK
authors.lastname: Murray
authors.affiliation: Department of Public Health Science and General Practice, Institute of Health Sciences, University of Oulu, Oulu, Finland; Faculty of Medicine, School of Public Health, Imperial College London, London, United Kingdom.
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Jarvelin
authors.affiliation: Public Health Genomics Unit, National Institute for Health and Welfare and Institute for Molecular Medicine, Helsinki, Finland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Ollila
authors.affiliation: Public Health Genomics Unit, National Institute for Health and Welfare and Institute for Molecular Medicine, Helsinki, Finland; Department of Psychiatry, Institute of Clinical Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Paunio
authors.affiliation: Department of Psychiatry, Centre for Clinical Neuroscience, University of Oulu, Oulu, Finland; Department of Psychiatry, Oulu University Hospital, Oulu, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Veijola
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D003071:Cognition; D005260:Female; D005387:Finland / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011597:Psychomotor Performance; D011618:Psychotic Disorders / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D017448:Receptors, Dopamine D2