Psychosis susceptibility gene ZNF804A and cognitive performance in schizophrenia.
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.
Walters
James T R
JT
Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, Wales.
Corvin
Aiden
A
Owen
Michael J
MJ
Williams
Hywel
H
Dragovic
Milan
M
Quinn
Emma M
EM
Judge
Róisín
R
Smith
Daniel J
DJ
Norton
Nadine
N
Giegling
Ina
I
Hartmann
Annette M
AM
Möller
Hans-Jürgen
HJ
Muglia
Pierandrea
P
Moskvina
Valentina
V
Dwyer
Sarah
S
O'Donoghue
Therese
T
Morar
Bharti
B
Cooper
Matthew
M
Chandler
David
D
Jablensky
Assen
A
Gill
Michael
M
Kaladjieva
Luba
L
Morris
Derek W
DW
O'Donovan
Michael C
MC
Rujescu
Dan
D
Donohoe
Gary
G
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*
D051741:Kruppel-Like Transcription Factors; C540527:ZNF804A protein, human