DAOA/G72 predicts the progression of prodromal syndromes to first episode psychosis

Mössner, Rainald; Schuhmacher, Anna; Wagner, Michael; Quednow, Boris B.; Frommann, Ingo; Kühn, Kai-Uwe; Schwab, Sibylle G.; Rietschel, Marcella; Falkai, Peter; Wölwer, Wolfgang; Ruhrmann, Stephan; Bechdolf, Andreas; Gaebel, Wolfgang; Klosterkötter, Joachim; Maier, Wolfgang
April 2010
European Archives of Psychiatry & Clinical Neuroscience;Apr2010, Vol. 260 Issue 3, p209
Academic Journal
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 (χ2 = 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 (χ2 = 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.


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