Influence of NOS1 on verbal intelligence and working memory in both patients with schizophrenia and healthy control subjects

Gary Donohoe, James Walters, Derek W. Morris, Emma M. Quinn, Roisín Judge, Nadine Norton, Ina Giegling, Annette M. Hartmann, Hans Jürgen Möller, Pierandrea Muglia, Hywel Williams, Valentina Moskvina, Rosemary Peel, Therese O'Donoghue, Michael J. Owen, Michael C. O'Donovan, Michael Gill, Dan Rujescu, Aiden Corvin

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1045-1054
Number of pages10
JournalArchives of General Psychiatry
Volume66
Issue number10
DOIs
StatePublished - Oct 2009
Externally publishedYes

Fingerprint

Intelligence
Short-Term Memory
Schizophrenia
Healthy Volunteers
Cognition
Genotype
Cognitive Reserve
Episodic Memory
Genome-Wide Association Study
Ambulatory Care
Ethnic Groups
Diagnostic and Statistical Manual of Mental Disorders
Single Nucleotide Polymorphism
Psychiatry
Inpatients
Population
Genes

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Influence of NOS1 on verbal intelligence and working memory in both patients with schizophrenia and healthy control subjects. / Donohoe, Gary; Walters, James; Morris, Derek W.; Quinn, Emma M.; Judge, Roisín; Norton, Nadine; Giegling, Ina; Hartmann, Annette M.; Möller, Hans Jürgen; Muglia, Pierandrea; Williams, Hywel; Moskvina, Valentina; Peel, Rosemary; O'Donoghue, Therese; Owen, Michael J.; O'Donovan, Michael C.; Gill, Michael; Rujescu, Dan; Corvin, Aiden.

In: Archives of General Psychiatry, Vol. 66, No. 10, 10.2009, p. 1045-1054.

Research output: Contribution to journalArticle

Donohoe, G, Walters, J, Morris, DW, Quinn, EM, Judge, R, Norton, N, Giegling, I, Hartmann, AM, Möller, HJ, Muglia, P, Williams, H, Moskvina, V, Peel, R, O'Donoghue, T, Owen, MJ, O'Donovan, MC, Gill, M, Rujescu, D & Corvin, A 2009, 'Influence of NOS1 on verbal intelligence and working memory in both patients with schizophrenia and healthy control subjects', Archives of General Psychiatry, vol. 66, no. 10, pp. 1045-1054. https://doi.org/10.1001/archgenpsychiatry.2009.139
Donohoe, Gary ; Walters, James ; Morris, Derek W. ; Quinn, Emma M. ; Judge, Roisín ; Norton, Nadine ; Giegling, Ina ; Hartmann, Annette M. ; Möller, Hans Jürgen ; Muglia, Pierandrea ; Williams, Hywel ; Moskvina, Valentina ; Peel, Rosemary ; O'Donoghue, Therese ; Owen, Michael J. ; O'Donovan, Michael C. ; Gill, Michael ; Rujescu, Dan ; Corvin, Aiden. / Influence of NOS1 on verbal intelligence and working memory in both patients with schizophrenia and healthy control subjects. In: Archives of General Psychiatry. 2009 ; Vol. 66, No. 10. pp. 1045-1054.
@article{cc46678480404480aa52f2f87a313c41,
title = "Influence of NOS1 on verbal intelligence and working memory in both patients with schizophrenia and healthy control subjects",
abstract = "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.",
author = "Gary Donohoe and James Walters and Morris, {Derek W.} and Quinn, {Emma M.} and Rois{\'i}n Judge and Nadine Norton and Ina Giegling and Hartmann, {Annette M.} and M{\"o}ller, {Hans J{\"u}rgen} and Pierandrea Muglia and Hywel Williams and Valentina Moskvina and Rosemary Peel and Therese O'Donoghue and Owen, {Michael J.} and O'Donovan, {Michael C.} and Michael Gill and Dan Rujescu and Aiden Corvin",
year = "2009",
month = "10",
doi = "10.1001/archgenpsychiatry.2009.139",
language = "English (US)",
volume = "66",
pages = "1045--1054",
journal = "JAMA Psychiatry",
issn = "2168-622X",
publisher = "American Medical Association",
number = "10",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=70349682718&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70349682718&partnerID=8YFLogxK

U2 - 10.1001/archgenpsychiatry.2009.139

DO - 10.1001/archgenpsychiatry.2009.139

M3 - Article

C2 - 19805695

AN - SCOPUS:70349682718

VL - 66

SP - 1045

EP - 1054

JO - JAMA Psychiatry

JF - JAMA Psychiatry

SN - 2168-622X

IS - 10

ER -