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Schizophr Res. 2015 May;164(1-3):181-6. doi: 10.1016/j.schres.2015.02.013. Epub 2015 Mar 13.

Genome-wide gene pathway analysis of psychotic illness symptom dimensions based on a new schizophrenia-specific model of the OPCRIT.

Author information

1
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth, University School of Medicine, VA, USA. Electronic address: ardocherty@vcu.edu.
2
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth, University School of Medicine, VA, USA.
3
Queen's University, Belfast, Ireland.
4
Center for Public Health, Belfast, Ireland.
5
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth, University School of Medicine, VA, USA; Washington Veterans Affairs Healthcare System, Washington D.C. USA; Georgetown University School of Medicine, Washington D.C. USA.

Abstract

Empirically derived phenotypic measurements have the potential to enhance gene-finding efforts in schizophrenia. Previous research based on factor analyses of symptoms has typically included schizoaffective cases. Deriving factor loadings from analysis of only narrowly defined schizophrenia cases could yield more sensitive factor scores for gene pathway and gene ontology analyses. Using an Irish family sample, this study 1) factor analyzed clinician-rated Operational Criteria Checklist items in cases with schizophrenia only, 2) scored the full sample based on these factor loadings, and 3) implemented genome-wide association, gene-based, and gene-pathway analysis of these SCZ-based symptom factors (final N=507). Three factors emerged from the analysis of the schizophrenia cases: a manic, a depressive, and a positive symptom factor. In gene-based analyses of these factors, multiple genes had q<0.01. Of particular interest are findings for PTPRG and WBP1L, both of which were previously implicated by the Psychiatric Genomics Consortium study of SCZ; results from this study suggest that variants in these genes might also act as modifiers of SCZ symptoms. Gene pathway analyses of the first factor indicated over-representation of glutamatergic transmission, GABA-A receptor, and cyclic GMP pathways. Results suggest that these pathways may have differential influence on affective symptom presentation in schizophrenia.

KEYWORDS:

Dimensional assessment; Gene enrichment; Gene pathway; Genetic; Modifier gene; OPCRIT; Schizophrenia; Symptoms

PMID:
25778617
PMCID:
PMC4409533
DOI:
10.1016/j.schres.2015.02.013
[Indexed for MEDLINE]
Free PMC Article

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