Influence of NOS1 on verbal intelligence and working memory in both patients with schizophrenia and healthy control subjects.
BACKGROUND
Human and animal studies have implicated the gene NOS1 in both cognition and schizophrenia susceptibility.


OBJECTIVE
To investigate whether a potential schizophrenia risk single-nucleotide polymorphism (rs6490121) identified in a recent genome-wide association study negatively influences cognition in patients with schizophrenia and healthy control subjects.


METHODS
A comparison of both cases and controls grouped according to NOS1 genotype (GG vs AG vs AA) on selected measures of cognition in 2 independent samples. We tested for association between NOS1 rs6490121 and cognitive functions known to be impaired in schizophrenia (IQ, episodic memory, working memory, and attentional control) in an Irish sample. We then sought to replicate the significant results in a German sample.


METHODS
Unrelated patients from general adult psychiatric inpatient and outpatient services and unrelated healthy volunteers from the general population were ascertained.


METHODS
Patients with DSM-IV-diagnosed schizophrenia and healthy control subjects from independent samples of Irish (cases, n = 349; controls, n = 230) and German (cases, n = 232; controls, n = 1344) nationality.


RESULTS
A main effect of NOS1 genotype on verbal IQ and working memory was observed in the Irish sample where the homozygous carriers of the schizophrenia risk G allele performed poorly compared with the other genotype groups. These findings were replicated in the German sample, again with the GG genotype carriers performing below other genotype groups. Post hoc analysis of additional IQ measures (full-scale and performance IQ) in the German sample revealed that NOS1 GG carriers underperformed on these measures also.


CONCLUSIONS
NOS1 is associated with clinically significant variation in cognition. Whether this is a mechanism by which schizophrenia risk is increased (eg, via an influence on cognitive reserve) is yet to be confirmed.
Donohoe
Gary
G
Neuropsychiatric Genetics Research Group, Department of Psychiatry, Trinity Health Sciences Bldg, St James's Hospital, Dublin 8, Ireland. gary.donohoe@tcd.ie
Walters
James
J
Morris
Derek W
DW
Quinn
Emma M
EM
Judge
Róisín
R
Norton
Nadine
N
Giegling
Ina
I
Hartmann
Annette M
AM
Möller
Hans-Jürgen
HJ
Muglia
Pierandrea
P
Williams
Hywel
H
Moskvina
Valentina
V
Peel
Rosemary
R
O'Donoghue
Therese
T
Owen
Michael J
MJ
O'Donovan
Michael C
MC
Gill
Michael
M
Rujescu
Dan
D
Corvin
Aiden
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D001288:Attention; D003072:Cognition Disorders / Q000175:diagnosis* / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D005858:Germany / Q000208:ethnology; D006801:Humans; D007360:Intelligence / Q000235:genetics; D007494:Ireland / Q000208:ethnology; D008297:Male; D008568:Memory; D008875:Middle Aged; D009483:Neuropsychological Tests; D052248:Nitric Oxide Synthase Type I / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000175:diagnosis* / Q000235:genetics*; D012565:Schizophrenic Psychology
C496320:NOS1 protein, human; D052248:Nitric Oxide Synthase Type I