title: Interaction between interleukin 3 and dystrobrevin-binding protein 1 in schizophrenia.
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, 1,350 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.
authors.affiliation: Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Todd L
authors.initials: TL
authors.lastname: Edwards
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.forename: Brandon
authors.initials: B
authors.lastname: Wormly
authors.forename: Brien
authors.initials: B
authors.lastname: Riley
authors.forename: F Anthony
authors.initials: FA
authors.lastname: O'Neill
authors.forename: Dermot
authors.initials: D
authors.lastname: Walsh
authors.forename: Marylyn D
authors.initials: MD
authors.lastname: Ritchie
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kendler
authors.forename: Xiangning
authors.initials: X
authors.lastname: Chen
mesh_terms: D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007377:Interleukin-3 / Q000235:genetics* / Q000502:physiology; D008297:Male; D008957:Models, Genetic; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology
chemical_list: D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D005819:Genetic Markers; D007377:Interleukin-3