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


CONCLUSIONS
Our results provide evidence for an association of SZ with SNPs at the 3' end of DTNBP1 in the samples studied.
Duan
Jubao
J
Center for Psychiatric Genetics, Department of Psychiatry and Behavioral Sciences, Evanston Northwestern Healthcare & Feinberg School of Medicine, Northwestern University, Evanston, Ill, USA. jduan@northwestern.edu
Martinez
Maria
M
Sanders
Alan R
AR
Hou
Cuiping
C
Burrell
Gregory J
GJ
Krasner
Aaron J
AJ
Schwartz
Daniel B
DB
Gejman
Pablo V
PV
D001741:Black or African American / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D044465:White People / Q000235:genetics
D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins