DAOA/G72 predicts the progression of prodromal syndromes to first episode psychosis.
The genetic factors determining the progression of prodromal syndromes to first episode schizophrenia have remained enigmatic to date. In a unique prospective multicentre trial, we assessed whether variants at the D-amino acid oxidase activator (DAOA)/G72 locus influence progression to psychosis. Young subjects with a prodromal syndrome were observed prospectively for up to 2 years to assess the incidence of progression to schizophrenia or first episode psychosis. Of the 82 probands with a prodromal syndrome, 21 probands experienced progression to psychosis within the observation period. Assessment of nine common variants in the DAOA/G72 locus yielded two variants with the predictive value for symptom progression: all four probands with the rs1341402 CC genotype developed psychosis compared with 17 out of 78 probands with the TT or CT genotypes (chi(2) = 12.348; df = 2; p = 0.002). The relative risk for progression to psychosis was significantly increased in the CC genotype: RR = 4.588 (95% CI = 2.175-4.588). Similarly, for rs778294, 50% of probands with the AA genotype, but only 22% of probands with a GG or GA genotype progressed to psychosis (chi(2) = 7.027; df = 2; p = 0.030). Moreover, haplotype analysis revealed a susceptibility haplotype for progression to psychosis. This is one of the first studies to identify a specific genetic factor for the progression of prodromal syndromes to schizophrenia, and further underscores the importance of the DAOA/G72 gene for schizophrenia.
Mössner
Rainald
R
Department of Psychiatry and Psychotherapy, University of Bonn, Sigmund-Freud-Strasse 25, 53105, Bonn, Germany. rainald.moessner@ukb.uni-bonn.de
Schuhmacher
Anna
A
Wagner
Michael
M
Quednow
Boris B
BB
Frommann
Ingo
I
Kühn
Kai-Uwe
KU
Schwab
Sibylle G
SG
Rietschel
Marcella
M
Falkai
Peter
P
Wölwer
Wolfgang
W
Ruhrmann
Stephan
S
Bechdolf
Andreas
A
Gaebel
Wolfgang
W
Klosterkötter
Joachim
J
Maier
Wolfgang
W
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D002352:Carrier Proteins / Q000235:genetics*; D016009:Chi-Square Distribution; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011618:Psychotic Disorders / Q000175:diagnosis / Q000235:genetics*; D055815:Young Adult
D002352:Carrier Proteins; C475071:DAOA protein, human; D047908:Intracellular Signaling Peptides and Proteins