Weak association of the platelet-derived growth factor beta (PDGFB) and PDGF receptor beta (PDGFRB) genes with schizophrenia and schizoaffective disorder.
Schizophrenia is a severe neuropsychiatric disorder with diverse characterization of symptoms. Extensive research has been performed to elucidate the etiology of schizophrenia. One of the most convincing hypotheses comes from the dopaminergic system although none of the core genes has been consistently positive in association studies.


OBJECTIVE
In this investigation, we explored the possibility that the genes for platelet-derived growth factor beta (PDGFB) and its receptor (PDGFRB) might play an important role in the development of schizophrenia based on previous reports pointing to their ability to interact with the dopamine D(2)/D(4) and NMDA receptors as well as their role in neurite outgrowth.


METHODS
We investigated the association of variants around these genes with schizophrenia and schizoaffective disorder in 104 small nuclear families using the Sib-Transmission Disequilibrium Test (TDT-STDT). Furthermore, quantitative trait analysis using family-based association test was applied to determine possible association of age at onset (AAO).


RESULTS
Allele G in PDGFRB(rs758588) was associated with AAO (P=0.019). An over-transmission of allele T in PDGFB(rs130650) polymorphism (P=0.043) and an over-transmission of allele A in PDGFRB(rs6865659) polymorphism (P=0.046) were observed. Furthermore, the combined TDT-STDT yielded consistent results.


CONCLUSIONS
Overall, PDGFB and PDGFRB genes might play a role in the etiology of schizophrenia.
Neurogenetics Section, Centre for Addiction and Mental Health, Clarke Division, Toronto, Canada.
Gwyneth
G
Zai
Clement
C
Zai
Arun
A
Tiwari
Nicole
N
King
Joanne
J
Braithwaite
Hubert
H
van Tol
James L
JL
Kennedy
D000328:Adult; D017668:Age of Onset; D000483:Alleles; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics*; D011618:Psychotic Disorders / Q000235:genetics*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics*; D011954:Receptors, Dopamine / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*
D020574:Proto-Oncogene Proteins c-sis; D011954:Receptors, Dopamine; D016194:Receptors, N-Methyl-D-Aspartate; D020797:Receptor, Platelet-Derived Growth Factor beta