Interaction between interleukin 3 and dystrobrevin-binding protein 1 in schizophrenia.
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.
Edwards
Todd L
TL
Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Wang
Xu
X
Chen
Qi
Q
Wormly
Brandon
B
Riley
Brien
B
O'Neill
F Anthony
FA
Walsh
Dermot
D
Ritchie
Marylyn D
MD
Kendler
Kenneth S
KS
Chen
Xiangning
X
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
D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D005819:Genetic Markers; D007377:Interleukin-3