Significant support for DAO as a schizophrenia susceptibility locus: examination of five genes putatively associated with schizophrenia.
BACKGROUND
Schizophrenia is a complex psychiatric disorder with a strong genetic component. Past linkage studies have implicated several chromosomal regions in the etiology of schizophrenia. Within these regions, several genes have been identified via candidate gene association studies as strong schizophrenia susceptibility loci, including DAO, DAOA, DISC1, DTNBP1, and RGS4.


METHODS
The present study attempted to replicate these association findings by analyzing a total of 120 markers across these genes in 311 schizophrenia subjects, 140 schizoaffective subjects, and 291 control subjects.


RESULTS
Our study found no association for DAOA and DTNBP1 with schizophrenia. Although no association was seen with DAOA and DTNBP1, several other markers in the other genes resulted in significant association with schizophrenia (p < .05). However, after a conservative Bonferroni correction for multiple testing, only one marker, rs3918346, within DAO remained significant (odds ratio = 1.71, confidence interval = 1.32-2.22, p = 4 x 10(-5)). This significant association was concordant with previous DAO genetic findings.


CONCLUSIONS
Our results significantly support DAO as a susceptibility locus for schizophrenia and offer some support for the implication of both RGS4 and DISC1 in the etiology of schizophrenia. However, we see no evidence to support either DAOA or DTNBP1 as schizophrenia disease loci.
Wood
Linda S
LS
Pharmacogenomics Molecular Profiling, Pfizer Global Research and Development, Groton, Connecticut 06340, USA. Linda.s.wood@pfizer.com
Pickering
Eve H
EH
Dechairo
Bryan M
BM
D002352:Carrier Proteins / Q000235:genetics; D002874:Chromosome Mapping; D003605:D-Amino-Acid Oxidase / Q000235:genetics*; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011618:Psychotic Disorders / Q000175:diagnosis / Q000235:genetics*; D020710:RGS Proteins / Q000235:genetics; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*
D002352:Carrier Proteins; C475071:DAOA protein, human; C412476:DISC1 protein, human; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D005819:Genetic Markers; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D020710:RGS Proteins; C098799:RGS4 protein; D003605:D-Amino-Acid Oxidase