TY  - JOUR
T1  - GEnetic association and brain morphology studies and the chromosome 8p22 pericentriolar material 1 (pcm1) gene in susceptibility to schizophrenia
AU  - Gurling HD, Critchley H, Datta SR, et al
Y1  - 2006/08/01
N1  - 10.1001/archpsyc.63.8.844
JO  - Archives of General Psychiatry
SP  - 844
EP  - 854
VL  - 63
IS  - 8
N2  - Context 
    There is evidence of linkage to a schizophrenia susceptibility locus on chromosome 8p21-22 found by several family linkage studies.Objectives 
    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.Design 
    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.Main Outcome Measures 
    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.
SN  - 0003-990X
M3  - doi: 10.1001/archpsyc.63.8.844
UR  - http://dx.doi.org/10.1001/archpsyc.63.8.844
ER  -