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
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
Author(s)
Gurling H.M., Critchley H., Datta S.R., McQuillin A., Blaveri E., Thirumalai S., Pimm J., Krasucki R., Kalsi G., Quested D., Lawrence J., Bass N., Choudhury K., Puri V., O'Daly O., Curtis D., Blackwood D., Muir W., Malhotra A.K., Buchanan R.W., Good C.D., Frackowiak R.S., Dolan R.J.
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.
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
Pubmed
Web of science
Create date
11/09/2011 18:07
Last modification date
20/08/2019 13:23
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