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Association study of DTNBP1 with schizophrenia in a US sample
Lingjun Zuo1, Xingguang Luo, Henry R Kranzler
1Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06516, USA.
Psychiatric Genetics
|October 30, 2009
Summary
The dystrobrevin-binding protein 1 (DTNBP1) gene is associated with schizophrenia risk in European-Americans. Specific DTNBP1 variations and their interactions, particularly in European-Americans, may influence schizophrenia development, with sex-modified effects observed.
Area of Science:
- Genetics
- Neuroscience
- Psychiatry
Background:
- The dystrobrevin-binding protein 1 (DTNBP1) locus has been implicated as a susceptibility region for schizophrenia.
- Previous replication attempts have yielded diverse findings, with several proposed pathways for dysbindin protein involvement in schizophrenia.
- This study addresses the need for robust association testing in diverse US populations.
Purpose of the Study:
- To investigate the association between DTNBP1 gene variations and schizophrenia risk in European-American and African-American populations.
- To employ advanced analytical methods to control for population stratification, admixture, and sex-specific effects.
- To identify specific DTNBP1 markers or haplotypes associated with schizophrenia risk.
Main Methods:
- Genotyping of six DTNBP1 markers and 38 ancestry-informative markers in 663 individuals (317 cases, 346 controls) using MassARRAY.
- Logistic regression analysis, including an extended structured association method, to compare allele, genotype, diplotype, and haplotype frequencies.
- Controlling for population stratification, admixture, sex-specific effects, and interaction effects.
Main Results:
- Nominal associations between specific DTNBP1 markers (rs1018381, rs909706) and schizophrenia were observed in European-Americans and African-Americans, respectively.
- These initial associations diminished after controlling for population stratification and admixture, and were not significant after multiple testing correction.
- However, regression analysis revealed significant associations for common diplotypes and haplotype interactions (GCCGCC/GCCGCC) in European-Americans, with sex-modified effects. Fine-mapping identified potential risk sites.
Conclusions:
- The DTNBP1 gene is implicated as a risk gene for schizophrenia in European-Americans.
- Specific variations and interactions within the DTNBP1 gene may contribute to schizophrenia risk in this population.
- Further research is warranted to elucidate the precise mechanisms of DTNBP1's role in schizophrenia pathogenesis.
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