Association study of the dystrobrevin-binding gene with schizophrenia in Australian and Indian samples.

Abstract

Numerous studies have reported association between variants in the dystrobrevin binding protein 1 (dysbindin) gene (DTNBP1) and schizophrenia. However, the pattern of results is complex and to date, no specific risk marker or haplotype has been consistently identified. The number of single nucleotide polymorphisms (SNPs) tested in these studies has ranged from 5 to 20. We attempted to replicate previous findings by testing 16 SNPs in samples of 41 Australian pedigrees, 194 Australian cases and 180 controls, and 197 Indian pedigrees. No globally significant evidence for association was observed in any sample, despite power calculations indicating sufficient power to replicate several previous findings. Possible explanations for our results include sample differences in background linkage disequilibrium and/or risk allele effect size, the presence of multiple risk alleles upon different haplotypes, or the presence of a single risk allele upon multiple haplotypes. Some previous associations may also represent false positives. Examination of Caucasian HapMap phase II genotype data spanning the DTNBP1 region indicates upwards of 40 SNPs are required to satisfactorily assess all nonredundant variation within DTNBP1 and its potential regulatory regions for association with schizophrenia. More comprehensive studies in multiple samples will be required to determine whether specific DTNBP1 variants function as risk factors for schizophrenia.

• Authors: Elizabeth G Holliday, Herlina Y Handoko, Michael R James, John J McGrath, Deborah A Nertney, Sujit Tirupati, Rangaswamy Thara, Douglas F Levinson, Nicholas K Hayward, Bryan J Mowry, Dale R Nyholt
• Journal: Twin research and human genetics : the official journal of the International Society for Twin Studies (Twin Res Hum Genet) Vol. 9 Issue 4 Pg. 531-9 (Aug 2006) ISSN: 1832-4274 [Print] England
• PMID: 16899160 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• DTNBP1 protein, human
• Dysbindin
• Dystrophin-Associated Proteins

Topics

• Alleles
• Australia
• Carrier Proteins (genetics)
• Case-Control Studies
• Dysbindin
• Dystrophin-Associated Proteins
• Female
• Genetic Predisposition to Disease
• Haplotypes
• Humans
• India
• Linkage Disequilibrium
• Male
• Polymorphism, Single Nucleotide
• Risk Factors
• Schizophrenia (genetics)
• White People