Interaction between interleukin 3 and dystrobrevin-binding protein 1 in schizophrenia

Todd L. Edwards, Xu Wang, Qi Chen, Brandon Wormly, Brien Riley, F. Anthony O'Neill, Dermot Walsh, Marylyn D. Ritchie, Kenneth S. Kendler, Xiangning Chen

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Schizophrenia is a common psychotic mental disorder that is believed to result from the effects of multiple genetic and environmental factors. In this study, we explored gene-gene interactions and main effects in both case-control (657 cases and 411 controls) and family-based (273 families, 1350 subjects) datasets of English or Irish ancestry. Fifty three markers in 8 genes were genotyped in the family sample and 44 markers in 7 genes were genotyped in the case-control sample. The Multifactor Dimensionality Reduction Pedigree Disequilibrium Test (MDR-PDT) was used to examine epistasis in the family dataset and a 3-locus model was identified (permuted p = 0.003). The 3-locus model involved the IL3 (rs2069803), RGS4 (rs2661319), and DTNBP1 (rs2619539) genes. We used MDR to analyze the case-control dataset containing the same markers typed in the RGS4, IL3 and DTNBP1 genes and found evidence of a joint effect between IL3 (rs31400) and DTNBP1 (rs760761) (cross-validation consistency 4/5, balanced prediction accuracy = 56.84%, p = 0.019). While this is not a direct replication, the results obtained from both the family and case-control samples collectively suggest that IL3 and DTNBP1 are likely to interact and jointly contribute to increase risk for schizophrenia. We also observed a significant main effect in DTNBP1, which survived correction for multiple comparisons, and numerous nominally significant effects in several genes.

Original languageEnglish (US)
Pages (from-to)208-217
Number of pages10
JournalSchizophrenia Research
Volume106
Issue number2-3
DOIs
StatePublished - Dec 2008

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Biological Psychiatry

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