Genotype-phenotype studies in bipolar disorder showing association between the DAOA/G30 locus and persecutory delusions: a first step toward a molecular genetic classification of psychiatric phenotypes.
OBJECTIVE
The authors previously reported an association between the D-amino acid oxidase activator (DAOA)/G30 locus and both schizophrenia and bipolar affective disorder. Given the presumed role of DAOA/G30 in the neurochemistry of psychosis and its localization in a schizophrenia and bipolar affective disorder linkage region (13q34), it was hypothesized that the bipolar affective disorder finding would be mainly due to an association with psychotic features.


METHODS
The marker/haplotype associations obtained in a subset of 173 bipolar affective disorder patients with psychotic features were similar to those in the overall patient group, suggesting that stratification on the basis of psychotic features in general might be too crude a procedure. The authors therefore tested whether confining caseness to specific psychotic features would improve detection of genotype-phenotype correlations.


RESULTS
In a logistic regression, "persecutory delusions" were found to be the only significant explanatory variable for the DAOA/G30 risk genotype among 21 OPCRIT symptoms of psychosis. The authors therefore tested for association between DAOA/G30 and bipolar affective disorder in the 90 cases with a history of persecutory delusions. Whereas this subset showed strong association (odds ratio=1.83 for the best marker), the remaining larger sample of 165 patients with no such history did not differ from comparison subjects, suggesting that the association between DAOA/G30 and bipolar affective disorder is due to persecutory delusions. This was confirmed in an independent study of 294 bipolar affective disorder patients and 311 comparison subjects from Poland, in which an association between bipolar affective disorder and DAOA/G30 was only seen when case definition was restricted to cases with persecutory delusions.


CONCLUSIONS
These data suggest that bipolar affective disorder with persecutory delusions constitutes a distinct subgroup of bipolar affective disorder that overlaps with schizophrenia.
Schulze
Thomas G
TG
Division of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health-J5, 68159 Mannheim, Germany. thomas.schulze@zi-mannheim.de
Ohlraun
Stephanie
S
Czerski
Piotr M
PM
Schumacher
Johannes
J
Kassem
Layla
L
Deschner
Monika
M
Gross
Magdalena
M
Tullius
Monja
M
Heidmann
Vivien
V
Kovalenko
Svetlana
S
Jamra
Rami Abou
RA
Becker
Tim
T
Leszczynska-Rodziewicz
Anna
A
Hauser
Joanna
J
Illig
Thomas
T
Klopp
Norman
N
Wellek
Stefan
S
Cichon
Sven
S
Henn
Fritz A
FA
McMahon
Francis J
FJ
Maier
Wolfgang
W
Propping
Peter
P
Nöthen
Markus M
MM
Rietschel
Marcella
M
D000328:Adult; D001714:Bipolar Disorder / Q000145:classification* / Q000235:genetics* / Q000523:psychology; D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D003702:Delusions / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology / Q000379:methods; D010259:Paranoid Disorders / Q000145:classification / Q000175:diagnosis / Q000235:genetics; D010641:Phenotype; D012559:Schizophrenia / Q000235:genetics; D012565:Schizophrenic Psychology
D002352:Carrier Proteins; C475071:DAOA protein, human; D005819:Genetic Markers; D047908:Intracellular Signaling Peptides and Proteins