TY - JOUR
T1 - Influence of NOS1 on verbal intelligence and working memory in both patients with schizophrenia and healthy control subjects
AU - Donohoe, Gary
AU - Walters, James
AU - Morris, Derek W.
AU - Quinn, Emma M.
AU - Judge, Roisín
AU - Norton, Nadine
AU - Giegling, Ina
AU - Hartmann, Annette M.
AU - Möller, Hans Jürgen
AU - Muglia, Pierandrea
AU - Williams, Hywel
AU - Moskvina, Valentina
AU - Peel, Rosemary
AU - O'Donoghue, Therese
AU - Owen, Michael J.
AU - O'Donovan, Michael C.
AU - Gill, Michael
AU - Rujescu, Dan
AU - Corvin, Aiden
PY - 2009/10
Y1 - 2009/10
N2 - Context: 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. Design: 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. Setting: Unrelated patients from general adult psychiatric inpatient and outpatient services and unrelated healthy volunteers from the general population were ascertained. Participants: 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 Gallele 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.
AB - Context: 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. Design: 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. Setting: Unrelated patients from general adult psychiatric inpatient and outpatient services and unrelated healthy volunteers from the general population were ascertained. Participants: 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 Gallele 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.
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U2 - 10.1001/archgenpsychiatry.2009.139
DO - 10.1001/archgenpsychiatry.2009.139
M3 - Article
C2 - 19805695
AN - SCOPUS:70349682718
SN - 0003-990X
VL - 66
SP - 1045
EP - 1054
JO - Archives of General Psychiatry
JF - Archives of General Psychiatry
IS - 10
ER -