title: Psychosis susceptibility gene ZNF804A and cognitive performance in schizophrenia.
abstract: BACKGROUND
  The Zinc Finger Protein 804A gene (ZNF804A) has been implicated in schizophrenia susceptibility by several genome-wide association studies. ZNF804A is brain expressed but of unknown function.
  
  
  OBJECTIVE
  To investigate whether the identified risk allele at the disease-associated single nucleotide polymorphism rs1344706 is associated with variation in neuropsychological performance in patients and controls.
  
  
  METHODS
  Comparison of cases and controls grouped according to ZNF804A genotype (AA vs AC vs CC) on selected measures of cognition in 2 independent samples.
  
  
  METHODS
  Unrelated patients from general adult psychiatric inpatient and outpatient services and unrelated healthy participants from the general population were ascertained.
  
  
  METHODS
  Patients with DSM-IV-diagnosed schizophrenia and healthy participants from independent samples of Irish (297 cases and 165 controls) and German (251 cases and 1472 controls) nationality.
  
  
  METHODS
  In this 2-stage study, we tested for an association between ZNF804A rs1344706 and cognitive functions known to be impaired in schizophrenia (IQ, episodic memory, working memory, and attention) in an Irish discovery sample. We then tested significant results in a German replication sample.
  
  
  RESULTS
  In the Irish samples, the ZNF804A genotype was associated with differences in episodic and working memory in patients but not in controls. These findings replicated in the same direction in the German samples. Furthermore, in both samples, when patients with a lower IQ were excluded, the association between ZNF804A and schizophrenia strengthened.
  
  
  CONCLUSIONS
  In a disorder characterized by heterogeneity, a risk variant at ZNF804A seems to delineate a patient subgroup characterized by relatively spared cognitive ability. Further work is required to establish whether this represents a discrete molecular pathogenesis that differs from that of other patient groups and whether this also has consequences for nosologic classification, illness course, or treatment.
authors.affiliation: Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, Wales.
authors.forename: James T R
authors.initials: JT
authors.lastname: Walters
authors.forename: Aiden
authors.initials: A
authors.lastname: Corvin
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: Hywel
authors.initials: H
authors.lastname: Williams
authors.forename: Milan
authors.initials: M
authors.lastname: Dragovic
authors.forename: Emma M
authors.initials: EM
authors.lastname: Quinn
authors.forename: Róisín
authors.initials: R
authors.lastname: Judge
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Smith
authors.forename: Nadine
authors.initials: N
authors.lastname: Norton
authors.forename: Ina
authors.initials: I
authors.lastname: Giegling
authors.forename: Annette M
authors.initials: AM
authors.lastname: Hartmann
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Möller
authors.forename: Pierandrea
authors.initials: P
authors.lastname: Muglia
authors.forename: Valentina
authors.initials: V
authors.lastname: Moskvina
authors.forename: Sarah
authors.initials: S
authors.lastname: Dwyer
authors.forename: Therese
authors.initials: T
authors.lastname: O'Donoghue
authors.forename: Bharti
authors.initials: B
authors.lastname: Morar
authors.forename: Matthew
authors.initials: M
authors.lastname: Cooper
authors.forename: David
authors.initials: D
authors.lastname: Chandler
authors.forename: Assen
authors.initials: A
authors.lastname: Jablensky
authors.forename: Michael
authors.initials: M
authors.lastname: Gill
authors.forename: Luba
authors.initials: L
authors.lastname: Kaladjieva
authors.forename: Derek W
authors.initials: DW
authors.lastname: Morris
authors.forename: Michael C
authors.initials: MC
authors.lastname: O'Donovan
authors.forename: Dan
authors.initials: D
authors.lastname: Rujescu
authors.forename: Gary
authors.initials: G
authors.lastname: Donohoe
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D005858:Germany / Q000208:ethnology; D006801:Humans; D007494:Ireland / Q000208:ethnology; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008297:Male; D008569:Memory Disorders / Q000175:diagnosis / Q000235:genetics; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D011618:Psychotic Disorders / Q000175:diagnosis / Q000235:genetics; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*; D012565:Schizophrenic Psychology; D044465:White People / Q000235:genetics; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: D051741:Kruppel-Like Transcription Factors; C540527:ZNF804A protein, human