Genetic association and brain morphology studies and the chromosome 8p22 pericentriolar material 1 (PCM1) gene in susceptibility to schizophrenia.
Details
Serval ID
serval:BIB_35F6118A2D00
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genetic association and brain morphology studies and the chromosome 8p22 pericentriolar material 1 (PCM1) gene in susceptibility to schizophrenia.
Journal
Archives of General Psychiatry
ISSN
0003-990X (Print)
ISSN-L
0003-990X
Publication state
Published
Issued date
2006
Volume
63
Number
8
Pages
844-854
Language
english
Notes
Publication types: Comparative Study ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
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.
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.
Keywords
Adult, Alleles, Atrophy/pathology, Autoantigens/genetics, Brain/pathology, Cell Cycle Proteins/genetics, Centrosome/metabolism, Centrosome/pathology, Chromosome Mapping, Chromosomes, Human, Pair 8/genetics, Female, Frontal Lobe/pathology, Genetic Markers, Genetic Predisposition to Disease/genetics, Humans, Linkage Disequilibrium, Magnetic Resonance Imaging, Male, Pedigree, Phenotype, Polymorphism, Genetic, Schizophrenia/genetics
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Web of science
Create date
11/09/2011 19:07
Last modification date
20/08/2019 14:23