Effects of a novel schizophrenia risk variant rs7914558 at CNNM2 on brain structure and attributional style

Emma Jane Rose, April Hargreaves, Derek Morris, Ciara Fahey, Daniela Tropea, Elizabeth Cummings, Carlo Caltagirone, Paola Bossù, Chiara Chiapponi, Fabrizio Piras, Gianfranco Spalletta, Michael Gill, Aiden Corvin, Gary Donohoe

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: A single nucleotide polymorphism (rs7914558) within the cyclin M2 (CNNM2) gene was recently identified as a common risk variant for schizophrenia. The mechanism by which CNNM2 confers risk is unknown. Aims: To determine the impact of the rs7914558 risk 'A' allele on measures of neurocognition, social cognition and brain structure. Method: Patients with schizophrenia (n = 400) and healthy controls (n = 160) completed measures of neuropsychological function and social cognition. Structural magnetic resonance imaging data were also acquired from an overlapping sample of Irish healthy controls (n = 159) and an independent sample of Italian patients (n = 82) and healthy controls (n = 39). Results: No effects of genotype on neuropsychological test performance were observed. However, a dosage effect of the risk allele was found for an index of social cognition (i.e. attributional style), such that risk status was associated with reduced self-serving bias across groups (GG>AG>AA, P<0.05). Using voxel-based morphometry to investigate neuroanatomical regions putatively supporting social cognition, risk carriers had relatively increased grey matter volume in the right temporal pole and right anterior cingulate cortex (Pcorrected<0.05) in the Irish healthy controls sample; neuroanatomical associations between CNNM2 and grey matter volume in anterior cingulate cortex were also observed in the Italian schizophrenia and healthy controls samples. Conclusions: Although the biological role of CNNM2 in schizophrenia remains unknown, these data suggest that this CNNM2 risk variant rs7914558 may have an impact on neural systems relevant to social cognition. How such effects may mediate the relationship between genotype and disease risk remains to be established.

Original languageEnglish (US)
Pages (from-to)115-121
Number of pages7
JournalBritish Journal of Psychiatry
Volume204
Issue number2
DOIs
StatePublished - Feb 1 2014

Fingerprint

Schizophrenia
Cognition
Brain
Gyrus Cinguli
Alleles
Genotype
Cyclins
Neuropsychological Tests
Single Nucleotide Polymorphism
Magnetic Resonance Imaging
Genes

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health

Cite this

Rose, Emma Jane ; Hargreaves, April ; Morris, Derek ; Fahey, Ciara ; Tropea, Daniela ; Cummings, Elizabeth ; Caltagirone, Carlo ; Bossù, Paola ; Chiapponi, Chiara ; Piras, Fabrizio ; Spalletta, Gianfranco ; Gill, Michael ; Corvin, Aiden ; Donohoe, Gary. / Effects of a novel schizophrenia risk variant rs7914558 at CNNM2 on brain structure and attributional style. In: British Journal of Psychiatry. 2014 ; Vol. 204, No. 2. pp. 115-121.
@article{9e68b91cc15f442086a17886dcc92fe2,
title = "Effects of a novel schizophrenia risk variant rs7914558 at CNNM2 on brain structure and attributional style",
abstract = "Background: A single nucleotide polymorphism (rs7914558) within the cyclin M2 (CNNM2) gene was recently identified as a common risk variant for schizophrenia. The mechanism by which CNNM2 confers risk is unknown. Aims: To determine the impact of the rs7914558 risk 'A' allele on measures of neurocognition, social cognition and brain structure. Method: Patients with schizophrenia (n = 400) and healthy controls (n = 160) completed measures of neuropsychological function and social cognition. Structural magnetic resonance imaging data were also acquired from an overlapping sample of Irish healthy controls (n = 159) and an independent sample of Italian patients (n = 82) and healthy controls (n = 39). Results: No effects of genotype on neuropsychological test performance were observed. However, a dosage effect of the risk allele was found for an index of social cognition (i.e. attributional style), such that risk status was associated with reduced self-serving bias across groups (GG>AG>AA, P<0.05). Using voxel-based morphometry to investigate neuroanatomical regions putatively supporting social cognition, risk carriers had relatively increased grey matter volume in the right temporal pole and right anterior cingulate cortex (Pcorrected<0.05) in the Irish healthy controls sample; neuroanatomical associations between CNNM2 and grey matter volume in anterior cingulate cortex were also observed in the Italian schizophrenia and healthy controls samples. Conclusions: Although the biological role of CNNM2 in schizophrenia remains unknown, these data suggest that this CNNM2 risk variant rs7914558 may have an impact on neural systems relevant to social cognition. How such effects may mediate the relationship between genotype and disease risk remains to be established.",
author = "Rose, {Emma Jane} and April Hargreaves and Derek Morris and Ciara Fahey and Daniela Tropea and Elizabeth Cummings and Carlo Caltagirone and Paola Boss{\`u} and Chiara Chiapponi and Fabrizio Piras and Gianfranco Spalletta and Michael Gill and Aiden Corvin and Gary Donohoe",
year = "2014",
month = "2",
day = "1",
doi = "10.1192/bjp.bp.113.131359",
language = "English (US)",
volume = "204",
pages = "115--121",
journal = "British Journal of Psychiatry",
issn = "0007-1250",
publisher = "Royal College of Psychiatrists",
number = "2",

}

Rose, EJ, Hargreaves, A, Morris, D, Fahey, C, Tropea, D, Cummings, E, Caltagirone, C, Bossù, P, Chiapponi, C, Piras, F, Spalletta, G, Gill, M, Corvin, A & Donohoe, G 2014, 'Effects of a novel schizophrenia risk variant rs7914558 at CNNM2 on brain structure and attributional style', British Journal of Psychiatry, vol. 204, no. 2, pp. 115-121. https://doi.org/10.1192/bjp.bp.113.131359

Effects of a novel schizophrenia risk variant rs7914558 at CNNM2 on brain structure and attributional style. / Rose, Emma Jane; Hargreaves, April; Morris, Derek; Fahey, Ciara; Tropea, Daniela; Cummings, Elizabeth; Caltagirone, Carlo; Bossù, Paola; Chiapponi, Chiara; Piras, Fabrizio; Spalletta, Gianfranco; Gill, Michael; Corvin, Aiden; Donohoe, Gary.

In: British Journal of Psychiatry, Vol. 204, No. 2, 01.02.2014, p. 115-121.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effects of a novel schizophrenia risk variant rs7914558 at CNNM2 on brain structure and attributional style

AU - Rose, Emma Jane

AU - Hargreaves, April

AU - Morris, Derek

AU - Fahey, Ciara

AU - Tropea, Daniela

AU - Cummings, Elizabeth

AU - Caltagirone, Carlo

AU - Bossù, Paola

AU - Chiapponi, Chiara

AU - Piras, Fabrizio

AU - Spalletta, Gianfranco

AU - Gill, Michael

AU - Corvin, Aiden

AU - Donohoe, Gary

PY - 2014/2/1

Y1 - 2014/2/1

N2 - Background: A single nucleotide polymorphism (rs7914558) within the cyclin M2 (CNNM2) gene was recently identified as a common risk variant for schizophrenia. The mechanism by which CNNM2 confers risk is unknown. Aims: To determine the impact of the rs7914558 risk 'A' allele on measures of neurocognition, social cognition and brain structure. Method: Patients with schizophrenia (n = 400) and healthy controls (n = 160) completed measures of neuropsychological function and social cognition. Structural magnetic resonance imaging data were also acquired from an overlapping sample of Irish healthy controls (n = 159) and an independent sample of Italian patients (n = 82) and healthy controls (n = 39). Results: No effects of genotype on neuropsychological test performance were observed. However, a dosage effect of the risk allele was found for an index of social cognition (i.e. attributional style), such that risk status was associated with reduced self-serving bias across groups (GG>AG>AA, P<0.05). Using voxel-based morphometry to investigate neuroanatomical regions putatively supporting social cognition, risk carriers had relatively increased grey matter volume in the right temporal pole and right anterior cingulate cortex (Pcorrected<0.05) in the Irish healthy controls sample; neuroanatomical associations between CNNM2 and grey matter volume in anterior cingulate cortex were also observed in the Italian schizophrenia and healthy controls samples. Conclusions: Although the biological role of CNNM2 in schizophrenia remains unknown, these data suggest that this CNNM2 risk variant rs7914558 may have an impact on neural systems relevant to social cognition. How such effects may mediate the relationship between genotype and disease risk remains to be established.

AB - Background: A single nucleotide polymorphism (rs7914558) within the cyclin M2 (CNNM2) gene was recently identified as a common risk variant for schizophrenia. The mechanism by which CNNM2 confers risk is unknown. Aims: To determine the impact of the rs7914558 risk 'A' allele on measures of neurocognition, social cognition and brain structure. Method: Patients with schizophrenia (n = 400) and healthy controls (n = 160) completed measures of neuropsychological function and social cognition. Structural magnetic resonance imaging data were also acquired from an overlapping sample of Irish healthy controls (n = 159) and an independent sample of Italian patients (n = 82) and healthy controls (n = 39). Results: No effects of genotype on neuropsychological test performance were observed. However, a dosage effect of the risk allele was found for an index of social cognition (i.e. attributional style), such that risk status was associated with reduced self-serving bias across groups (GG>AG>AA, P<0.05). Using voxel-based morphometry to investigate neuroanatomical regions putatively supporting social cognition, risk carriers had relatively increased grey matter volume in the right temporal pole and right anterior cingulate cortex (Pcorrected<0.05) in the Irish healthy controls sample; neuroanatomical associations between CNNM2 and grey matter volume in anterior cingulate cortex were also observed in the Italian schizophrenia and healthy controls samples. Conclusions: Although the biological role of CNNM2 in schizophrenia remains unknown, these data suggest that this CNNM2 risk variant rs7914558 may have an impact on neural systems relevant to social cognition. How such effects may mediate the relationship between genotype and disease risk remains to be established.

UR - http://www.scopus.com/inward/record.url?scp=84893527986&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84893527986&partnerID=8YFLogxK

U2 - 10.1192/bjp.bp.113.131359

DO - 10.1192/bjp.bp.113.131359

M3 - Article

VL - 204

SP - 115

EP - 121

JO - British Journal of Psychiatry

JF - British Journal of Psychiatry

SN - 0007-1250

IS - 2

ER -