Failure to confirm allelic and haplotypic association between markers at the chromosome 6p22.3 dystrobrevin-binding protein 1 (DTNBP1) locus and schizophrenia.
BACKGROUND
Previous linkage and association studies may have implicated the Dystrobrevin-binding protein 1 (DTNBP1) gene locus or a gene in linkage disequilibrium with DTNBP1 on chromosome 6p22.3 in genetic susceptibility to schizophrenia.


METHODS
We used the case control design to test for of allelic and haplotypic association with schizophrenia in a sample of four hundred and fifty research subjects with schizophrenia and four hundred and fifty ancestrally matched supernormal controls. We genotyped the SNP markers previously found to be significantly associated with schizophrenia in the original study and also other markers found to be positive in subsequent studies.


RESULTS
We could find no evidence of allelic, genotypic or haplotypic association with schizophrenia in our UK sample.


CONCLUSIONS
The results suggest that the DTNBP1 gene contribution to schizophrenia must be rare or absent in our sample. The discrepant allelic association results in previous studies of association between DTNBP1 and schizophrenia could be due population admixture. However, even positive studies of European populations do not show any consistent DTNBP1 alleles or haplotypes associated with schizophrenia. Further research is needed to resolve these issues. The possible confounding of linkage with association in family samples already showing linkage at 6p22.3 might be revealed by testing genes closely linked to DTNBP1 for allelic association and by restricting family based tests of association to only one case per family.
Datta
Susmita R
SR
Molecular Psychiatry Laboratory, Department of Mental Health Sciences, University College London Medical School, Windeyer Institute of Medical Sciences, 46 Cleveland Street, London, W1T 4JF, UK. h.gurling@ucl.ac.uk.
McQuillin
Andrew
A
Puri
Vinay
V
Choudhury
Khalid
K
Thirumalai
Srinivasa
S
Lawrence
Jacob
J
Pimm
Jonathan
J
Bass
Nicholas
N
Lamb
Graham
G
Moorey
Helen
H
Morgan
Jenny
J
Punukollu
Bhaskar
B
Kandasami
Gomathinayagam
G
Kirwin
Simon
S
Sule
Akeem
A
Quested
Digby
D
Curtis
David
D
Gurling
Hugh Md
HM