title: Genetic association and brain morphology studies and the chromosome 8p22 pericentriolar material 1 (PCM1) gene in susceptibility to schizophrenia.
abstract: BACKGROUND
  There is evidence of linkage to a schizophrenia susceptibility locus on chromosome 8p21-22 found by several family linkage studies.
  
  
  OBJECTIVE
  To fine map and identify a susceptibility gene for schizophrenia on chromosome 8p22 and to investigate the effect of this genetic susceptibility on an endophenotype of abnormal brain structure using magnetic resonance imaging.
  
  
  METHODS
  Fine mapping and identification of a chromosome 8p22 susceptibility gene was carried out by finding linkage disequilibrium between genetic markers and schizophrenia in multiply affected families, a case-control sample, and a trio sample. Variation in brain morphology associated with pericentriolar material 1 (PCM1) alleles was examined using voxel-based morphometry and statistical parametric mapping with magnetic resonance imaging. Setting and Patients A family sample of 13 large families multiply affected with schizophrenia, 2 schizophrenia case-control samples from the United Kingdom and Scotland, and a sample of schizophrenic trios from the United States containing parents and 1 affected child with schizophrenia.
  
  
  METHODS
  Tests of transmission disequilibrium between PCM1 locus polymorphisms and schizophrenia using a family sample and tests of allelic association in case-control and trio samples. Voxel-based morphometry using statistical parametric mapping.
  
  
  RESULTS
  The family and trio samples both showed significant transmission disequilibrium between marker D85261 in the PCM1 gene locus and schizophrenia. The case-control sample from the United Kingdom also found significant allelic association between PCM1 gene markers and schizophrenia. Voxel-based morphometry of cases who had inherited a PCM1 genetic susceptibility showed a significant relative reduction in the volume of orbitofrontal cortex gray matter in comparison with patients with non-PCM1-associated schizophrenia, who, by contrast, showed gray matter volume reduction in the temporal pole, hippocampus, and inferior temporal cortex.
  
  
  CONCLUSIONS
  The PCM1 gene is implicated in susceptibility to schizophrenia and is associated with orbitofrontal gray matter volumetric deficits.
authors.affiliation: Molecular Psychiatry Laboratory, Department of Mental Health Sciences, University College London Medical School, Windeyer Institute of Medical Sciences, London, United Kingdom. h.gurling@ucl.ac.uk
authors.forename: Hugh M D
authors.initials: HM
authors.lastname: Gurling
authors.forename: Hugo
authors.initials: H
authors.lastname: Critchley
authors.forename: Susmita R
authors.initials: SR
authors.lastname: Datta
authors.forename: Andrew
authors.initials: A
authors.lastname: McQuillin
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Blaveri
authors.forename: Srinivasa
authors.initials: S
authors.lastname: Thirumalai
authors.forename: Jonathan
authors.initials: J
authors.lastname: Pimm
authors.forename: Robert
authors.initials: R
authors.lastname: Krasucki
authors.forename: Gursharan
authors.initials: G
authors.lastname: Kalsi
authors.forename: Digby
authors.initials: D
authors.lastname: Quested
authors.forename: Jacob
authors.initials: J
authors.lastname: Lawrence
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bass
authors.forename: Khalid
authors.initials: K
authors.lastname: Choudhury
authors.forename: Vinay
authors.initials: V
authors.lastname: Puri
authors.forename: Owen
authors.initials: O
authors.lastname: O'Daly
authors.forename: David
authors.initials: D
authors.lastname: Curtis
authors.forename: Douglas
authors.initials: D
authors.lastname: Blackwood
authors.forename: Walter
authors.initials: W
authors.lastname: Muir
authors.forename: Anil K
authors.initials: AK
authors.lastname: Malhotra
authors.forename: Robert W
authors.initials: RW
authors.lastname: Buchanan
authors.forename: Catriona D
authors.initials: CD
authors.lastname: Good
authors.forename: Richard S J
authors.initials: RS
authors.lastname: Frackowiak
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Dolan
mesh_terms: D000328:Adult; D000483:Alleles; D001284:Atrophy / Q000473:pathology; D001324:Autoantigens / Q000235:genetics*; D001921:Brain / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000235:genetics*; D018385:Centrosome / Q000378:metabolism / Q000473:pathology*; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008279:Magnetic Resonance Imaging; D008297:Male; D010375:Pedigree; D010641:Phenotype; D011110:Polymorphism, Genetic; D012559:Schizophrenia / Q000235:genetics*
chemical_list: D001324:Autoantigens; D018797:Cell Cycle Proteins; D005819:Genetic Markers; C086074:PCM1 protein, human