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


Mössner, R; Schumacher, A; Wagner, M; Quednow, B B; Frommann, I; Kühn, K U; Schwab, S G; Rietschel, M; Falkai, P; Wölwer, W; Ruhrmann, S; Bechdolf, A; Gaebel, W; Klosterkötter, J; Maier, W (2010). DAOA/G72 predicts the progression of prodromal syndromes to first episode psychosis. European Archives of Psychiatry and Clinical Neuroscience, 260(3):209-215.

Abstract

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 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 predictive value for symptom progression: all four probands with the rs1341402 CC genotype developed psychosis, compared to 17 out of 78 probands with the TT or CT genotypes (chi2 =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% C.I.=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 (chi2 = 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.

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 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 predictive value for symptom progression: all four probands with the rs1341402 CC genotype developed psychosis, compared to 17 out of 78 probands with the TT or CT genotypes (chi2 =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% C.I.=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 (chi2 = 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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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Clinic for Psychiatry, Psychotherapy, and Psychosomatics
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:April 2010
Deposited On:16 Dec 2009 08:32
Last Modified:05 Apr 2016 13:39
Publisher:Springer
ISSN:0940-1334
Additional Information:The original publication is available at www.springerlink.com
Publisher DOI:10.1007/s00406-009-0044-y
PubMed ID:19763662
Permanent URL: http://doi.org/10.5167/uzh-25941

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