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. 2007;64(2):97-106.
doi: 10.1159/000101961. Epub 2007 May 2.

DTNBP1 (Dystrobrevin binding protein 1) and schizophrenia: association evidence in the 3' end of the gene

Jubao Duan  1 , Maria Martinez, Alan R Sanders, Cuiping Hou, Gregory J Burrell, Aaron J Krasner, Daniel B Schwartz, Pablo V Gejman
Affiliations

DTNBP1 (Dystrobrevin binding protein 1) and schizophrenia: association evidence in the 3' end of the gene

Jubao Duan et al. Hum Hered. 2007.

Abstract

Objectives: Dysbindin (DTNBP1) has been identified as a susceptibility gene for schizophrenia (SZ) through a positional approach. However, a variety of single nucleotide polymorphisms (SNPs) and haplotypes, in different parts of the gene, have been reported to be associated in different samples, and a precise molecular mechanism of disease remains to be defined. We have performed an association study with two well-characterized family samples not previously investigated at the DTNBP1 locus.

Methods: We examined 646 subjects in 136 families with SZ, largely of European ancestry (EA), genotyping 26 SNPs in DTNBP1.

Results: Three correlated markers (rs875462, rs760666, and rs7758659) at the 3' region of DTNBP1 showed evidence for association to SZ (p = 0.004), observed in both the EA (p = 0.031) and the African American (AA) subset (p = 0.045) with the same over-transmitted allele. The most significant haplotype in our study was rs7758659-rs3213207 (global p = 0.0015), with rs3213207 being the most frequently reported associated marker in previous studies. A non-conservative missense variant (Pro272Ser) in the 3' region of DTNBP1 that may impair DTNBP1 function was more common in SZ probands (8.2%) than in founders (5%) and in dbSNP (2.1%), but did not reach statistical significance.

Conclusion: Our results provide evidence for an association of SZ with SNPs at the 3' end of DTNBP1 in the samples studied.

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Figures

Fig. 1
Fig. 1
Alternative transcripts for DTNBP1 and relative positions of the tested SNPs in this study. Exons are numbered in the order of the typical 10-exon transcript variant (NM_032122). 1a, 6a, b, 7a–c indicate cryptic exons. 1-ex, 3-ex, 6-ex, 8-ex, 9-ex, and 10-ex represent exons with variable boundaries. All the information for 15 transcripts is taken from AceView, an integrated view of human genes reconstructed by co-alignment of all publicly available mRNAs and expressed sequence tags (ESTs) on the genome sequence, updated on November 29, 2004 (www.ncbi.nlm.nih.gov/IEB/Research/Acembly/). Positively associated SNPs are indicated by an asterisk.
Fig. 2
Fig. 2
LD structure of DTNBP1 in EA founders. a Pair wise LD structure is shown as matrix according to D' and LOD at the bottom. Genomic positions are according to the NCBI Build 35 of the human genome assembly (genome.ucsc.edu; May 2004 freeze). We generated the figure by the LocusView program (www.broad.mit.edu/mpg/locusview/). b r2 among different markers. Within the long LD block (D'), seven LD bins measured by r2 are indicated with A to G.
See this image and copyright information in PMC

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