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Analysis of treatment-resistant schizophrenia and 384 markers from candidate genes.
MedLine Citation:
PMID:  23047292     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
The treatment of patients with schizophrenia who fail to respond to antipsychotics is a major challenge and the proportion of treatment-resistant patients is estimated to be 20 to 40%. There are few genetic association studies that have compared resistant versus non-resistant schizophrenic patients; however, many genetic association studies focusing on antipsychotic response have been published. This contribution investigates the genetics of treatment-resistant schizophrenia, testing 384 candidate gene loci related to the neurobiology of the disease. First, we identified a subgroup of treatment-resistant patients in a sample of 240 schizophrenia patients using the American Psychiatric Association criteria and then we genotyped all patients using a custom Illumina Bead Chip comprising of 384 single nucleotide polymorphisms. We screened all markers for nominal significance and for statistical significance after multiple-testing correction. The most significant single nucleotide polymorphism was the rs2152324 marker in the NALCN gene (P=0.004); however, after the FDR correction, the P-value was not significant. Our analysis of 384 markers across candidate genes did not indicate any robust association with treatment-resistant schizophrenia. However, this phenotype can be assessed retrospectively in cross-sectional studies and these preliminary results point out the importance of choosing alternative phenotypes in psychiatric pharmacogenetics.
Authors:
Celine Teo; Clement Zai; Carol Borlido; Carmine Tomasetti; John Strauss; Takahiro Shinkai; Bernard Le Foll; Albert Wong; James L Kennedy; Vincenzo De Luca
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Pharmacogenetics and genomics     Volume:  22     ISSN:  1744-6880     ISO Abbreviation:  Pharmacogenet. Genomics     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101231005     Medline TA:  Pharmacogenet Genomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  807-11     Citation Subset:  IM    
Affiliation:
aCentre for Addiction and Mental Health (CAMH), Department of Psychiatry, University of Toronto, Ontario, Toronto bDepartment of Neuroscience, University of Naples 'Federico II', Naples, Italy cDepartment of Psychiatry, University of Occupational and Environmental, Health, Yahatanishi-ku, Kitakyushu, Japan.
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