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.
  
  
  OBJECTIVE
  To determine the impact of the rs7914558 risk 'G' allele [corrected] on measures of neurocognition, social cognition and brain structure.
  
  
  METHODS
  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.
authors: Emma Jane Rose, PhD, Neuropsychiatric Genetics Group, Department of Psychiatry and Trinity College Institute of Neuroscience, Trinity College Dublin, Ireland, and TSTPP/MEGEH, RTI International, Baltimore, Maryland, USA; April Hargreaves, MSc, Derek Morris, PhD, Ciara Fahey, MSc, Daniela Tropea, PhD, Elizabeth Cummings, MD, Neuropsychiatric Genetics Group, Department of Psychiatry, Trinity College Dublin, Ireland; Carlo Caltagirone, MD, IRCCS Santa Lucia Foundation, Department of Clinical and Behavioural Neurology and Department of Neuroscience, Tor Vergata University, Rome, Italy; Paola Bossù, PhD, Chiara Chiapponi, PhD, Fabrizio Piras, PhD, Gianfranco Spalletta, MD, PhD, IRCCS Santa Lucia Foundation, Department of Clinical and Behavioural Neurology, Rome, Italy; Michael Gill, MD, Aiden Corvin, MD, Neuropsychiatric Genetics Group, Department of Psychiatry and Trinity College Institute of Neuroscience, Trinity College Dublin, Ireland; Gary Donohoe, PhD, Neuropsychiatric Genetics Group, Department of Psychiatry and Trinity College Institute of Neuroscience, Trinity College Dublin, and School of Psychology, National University of Ireland, Galway, Ireland.
authors: Emma Jane
authors: EJ
authors: Rose
authors: April
authors: A
authors: Hargreaves
authors: Derek
authors: D
authors: Morris
authors: Ciara
authors: C
authors: Fahey
authors: Daniela
authors: D
authors: Tropea
authors: Elizabeth
authors: E
authors: Cummings
authors: Carlo
authors: C
authors: Caltagirone
authors: Paola
authors: P
authors: Bossù
authors: Chiara
authors: C
authors: Chiapponi
authors: Fabrizio
authors: F
authors: Piras
authors: Gianfranco
authors: G
authors: Spalletta
authors: Michael
authors: M
authors: Gill
authors: Aiden
authors: A
authors: Corvin
authors: Gary
authors: G
authors: Donohoe
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000704:Analysis of Variance; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D027682:Cation Transport Proteins; D016213:Cyclins / Q000235:genetics / Q000502:physiology*; D056348:Emotional Intelligence / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006179:Gyrus Cinguli / Q000473:pathology; D006801:Humans; D007389:Internal-External Control; D007494:Ireland; D007558:Italy; D015810:Linkage Disequilibrium; D008279:Magnetic Resonance Imaging / Q000379:methods; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D009929:Organ Size; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology; D012565:Schizophrenic Psychology; D013702:Temporal Lobe / Q000473:pathology; D055815:Young Adult
chemical_list: C558175:CNNM2 protein, human; D027682:Cation Transport Proteins; D016213:Cyclins