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

Anna R. Docherty*, T. Bernard Bigdeli, Alexis C. Edwards, Silviu Bacanu, Donghyung Lee, Michael C. Neale, Brandon K. Wormley, Dermot Walsh, F. Anthony O'Neill, Brien P. Riley, Kenneth S. Kendler, Ayman H. Fanous

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)181-186
Number of pages6
JournalSchizophrenia research
Volume164
Issue number1-3
Early online date13 Mar 2015
DOIs
Publication statusPublished - May 2015

Keywords

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

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Fingerprint Dive into the research topics of 'Genome-wide gene pathway analysis of psychotic illness symptom dimensions based on a new schizophrenia-specific model of the OPCRIT'. Together they form a unique fingerprint.

Cite this