The DAOA/G30 locus and affective disorders: haplotype based association study in a polydiagnostic approach.
BACKGROUND
The DAOA/G30 (D-amino acid oxidase activator) gene complex at chromosomal region 13q32-33 is one of the most intriguing susceptibility loci for the major psychiatric disorders, although there is no consensus about the specific risk alleles or haplotypes across studies.


METHODS
In a case-control sample of German descent (affective psychosis: n = 248; controls: n = 188) we examined seven single nucleotide polymorphisms (SNPs) around DAOA/G30 (rs3916966, rs1935058, rs2391191, rs1935062, rs947267, rs3918342, and rs9558575) for genetic association in a polydiagnostic approach (ICD 10; Leonhard's classification).


RESULTS
No single marker showed evidence of overall association with affective disorder neither in ICD10 nor Leonhard's classification. Haplotype analysis revealed no association with recurrent unipolar depression or bipolar disorder according to ICD10, within Leonhard's classification manic-depression was associated with a 3-locus haplotype (rs2391191, rs1935062, and rs3916966; P = 0.022) and monopolar depression with a 5-locus combination at the DAOA/G30 core region (P = 0.036).


CONCLUSIONS
Our data revealed potential evidence for partially overlapping risk haplotypes at the DAOA/G30 locus in Leonhard's affective psychoses, but do not support a common genetic contribution of the DAOA/G30 gene complex to the pathogenesis of affective disorders.
Gawlik
Micha
M
Department of Psychiatry and Psychotherapy, University of Würzburg, Füchsleinstrasse 15, Würzburg, Germany. gawlik_m@klinik.uni-wuerzburg.de
Wehner
Ingeborg
I
Mende
Meinhard
M
Jung
Sven
S
Pfuhlmann
Bruno
B
Knapp
Michael
M
Stöber
Gerald
G
D000328:Adult; D000483:Alleles; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002874:Chromosome Mapping / Q000706:statistics & numerical data; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D003866:Depressive Disorder / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies / Q000706:statistics & numerical data; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
D002352:Carrier Proteins; C475071:DAOA protein, human; D005819:Genetic Markers; D047908:Intracellular Signaling Peptides and Proteins