Positional pathway screen of wnt signaling genes in schizophrenia: association with DKK4.
BACKGROUND
Wnt signaling has been implicated in schizophrenia from studies of gene expression in patients, from an understanding of the function of reported susceptibility genes and from experimental studies of psychoactive drugs. This diverse evidence suggests that wnt signaling genes, defined as pathway participants, modifiers or targets, are good candidates as susceptibility factors.


METHODS
We performed a combined positional and candidate association screen by identifying known wnt signaling genes in regions linked to schizophrenia. In a staged study we examined over 50 single nucleotide polymorphisms (SNPs) in 28 wnt signaling genes, first in trios of Chinese origin and then in a case-control series from Hong Kong.


RESULTS
In both sets, Dickkopf 4 (DKK4) was associated with schizophrenia - with an odds ratio of 3.9 (p < .01, CI = 1.3-11.1) in the combined sample.


CONCLUSIONS
As DKK family members have previously been found to show altered expression in schizophrenia brain and to bind to neuregulin, this finding suggests that DKK4 may play a role in schizophrenia pathogenesis.
Proitsi
Petroula
P
Department of Psychological Medicine, Institute of Psychiatry, King's College, London, United Kingdom.
Li
Tao
T
Hamilton
Gillian
G
Di Forti
Marta
M
Collier
David
D
Killick
Richard
R
Chen
Ronald
R
Sham
Pak
P
Murray
Robin
R
Powell
John
J
Lovestone
Simon
S
D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China; D005192:Family Health; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism*
C442333:DKK4 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D051153:Wnt Proteins